A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several...Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).展开更多
The blood-brain barrier(BBB)is a major challenge in drug delivery for the treatment of central nervous system diseases.Walnut derived peptide TWLPLPR(TW-7)has been proved to promote neuronal mitochondrial autophagy an...The blood-brain barrier(BBB)is a major challenge in drug delivery for the treatment of central nervous system diseases.Walnut derived peptide TWLPLPR(TW-7)has been proved to promote neuronal mitochondrial autophagy and enhance hippocampal neuronal synaptic plasticity,thereby improving learning and memory abilities in mice.We investigated the internalization mechanism and intracellular transport pathway for the walnut-derived peptide,TW-7,using b End.3 cells in an in vitro BBB model system.TW-7 was taken up by the b End.3 cells in a concentration-,temperature-,and energy-dependent manner;this involved increases in caveolin-1 and caveolin-2 protein expression and phosphorylation and inhibition of P-glycoprotein-mediated efflux.Subcellular localization of TW-7 in b End.3 cells was observed,indicating that the plasma membrane,endoplasmic reticulum,Golgi apparatus,lysosomes,and mitochondria participated in intracellular trafficking and that the peptide escaped from lysosomes over time.Caveolae may be critical for TW-7 uptake by brain microvascular endothelial cells,assisting TW-7 to cross the BBB.The results of this study provide a theoretical basis for the mechanism of active peptide penetrating the BBB,and provide a reference for developing neuroprotective active peptide products.展开更多
The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a se...The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.展开更多
Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonst...Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.展开更多
Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically s...Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically significant for improving health.This weight loss can be achieved through pharmacotherapy,including glucagon-like peptide 1(GLP-1)receptor agonists,GLP-1/glucosedependent insulinotropic peptide dual receptor agonists,and GLP-1/glucosedependent insulinotropic peptide/glucagon triple receptor agonists(such as semaglutide,tirzepatide,and retatrutide,respectively).While much of the weight loss comes from fat mass,these treatments also result in the loss of lean mass,including muscle.This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia.Therefore,the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass,ideally promoting muscle gain.Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction,which may play a crucial role in preserving both muscle mass and function.We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes.Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.展开更多
Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in devel...Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in development,peptides stand out for their unique advantages,including minimal immunogenicity,high tissue penetration,and ease of modification.Their small size,specificity,and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively.Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery,improving tumor imaging,and reducing adverse effects.With cancer responsible for millions of deaths worldwide,the development of peptide-based therapeutics offers new hope in addressing the limitations of current treatments.As detailed studies on different aspects of targeting peptides are crucial for optimizing drug development,this review provides a comprehensive overview of the literature on tumor-targeting peptides,including their structure,sources,modes of action,and their application in cancer therapy—both as standalone agents and in fusion drugs.Additionally,various computational tools for peptide-based tumor-targeting drug design and validation are explored.The promising results from these studies highlight peptides as ideal candidates for targeted cancer therapies,offering valuable insights for researchers and accelerating the discovery of novel anti-tumor peptide base drug candidates.展开更多
Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural ...Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide combinations of the canonical residues has been previously reported.However,with increasing computational power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the complete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify potential small peptide inhibitors.展开更多
Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety...Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.展开更多
Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen so...Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.展开更多
Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ab...Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.展开更多
Nine peptide-modified Salen-Co(Ⅱ)complexes based on three Salen ligand frameworks SA1~SA3 and four oligopeptides P1~P4 have been prepared.Their catalytic activities were examined through a model hydrohydrazination of...Nine peptide-modified Salen-Co(Ⅱ)complexes based on three Salen ligand frameworks SA1~SA3 and four oligopeptides P1~P4 have been prepared.Their catalytic activities were examined through a model hydrohydrazination of cinnamic alcohol with azodicarboxylate.While peptide-modified Salen-Co(Ⅱ)complexes derived from SA1 are ineffective,its parent 1SalenCo and those based on SA2 and SA3 are excellent catalyst for this reaction.These results demonstrate that peptide ligands significantly modulate the catalytic activity of SalenCo(Ⅱ)complexes,particularly at lower temperatures,likely due to hydrogen-bonding interactions.展开更多
The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidom...The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidomics and bioinformatics were used to screen flavor peptides from Inner Mongolian cheese and further assess their antioxidant and angiotensin I-converting enzyme(ACE)inhibitory properties.According to sensory data,YH8 and IL7 had detectable bitter tastes with low thresholds of 0.03 and 0.06 mmol/L,respectively.With an umami threshold range of 0.24‒0.81 mmol/L,VQ6,FK13,HP13 and QT14 exhibited a range of flavors dominated by umami,including sweet,bitter,salty,sour and kokumi.Antioxidant activity wise,YH8,VQ6,HP13 and QT14 were well represented.The above-mentioned peptides all had some ACE inhibitory effect.The bitter peptide IL7(IC_(50)=0.08 mmol/L)had the highest level of ACE inhibitory activity,followed by YH8(IC_(50)=0.33 mmol/L).These multi-functional peptides,which have been assessed for bioactive and taste features in Inner Mongolian cheese,may have positive impacts on health and harmonize the cheese’s overall flavor.These results suggest that some flavor peptides produced in fermented foods might be with bioactivities while providing a basis for the exploration and application of multi-functional peptides.展开更多
Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is ge...Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.展开更多
Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-ad...Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.展开更多
Oxidative stress arises from disruption of the balance between reactive oxygen species(ROS)production and detoxification and constitutes a fundamental driver of diverse pathological diseases.Skin photoaging is a well-...Oxidative stress arises from disruption of the balance between reactive oxygen species(ROS)production and detoxification and constitutes a fundamental driver of diverse pathological diseases.Skin photoaging is a well-recognized example,primarily driven by chronic ultraviolet(UV)exposure and marked by progressive structural and functional deterioration.UV-induced ROS accelerate macromolecular degradation and impair epidermal and dermal barrier integrity,highlighting the urgent need for effective antioxidant interventions.Antioxidant peptides(AOPs),whether naturally occurring or synthetically engineered,have shown considerable potential in mitigating ROS-induced cellular damage.Amphibians,which possess highly permeable skin and are continuously challenged by fluctuating environmental conditions,represent a rich source of bioactive peptides with potent antioxidant properties.In particular,AOPs isolated from amphibian skin secretions demonstrate notable efficacy in ROS scavenging and mitigation of oxidative damage,offering promising candidates for anti-photoaging therapies.This review provides an integrated overview of ROS generation and signaling,the molecular mechanisms linking oxidative stress to skin photoaging,and the emerging biomedical potential of amphibian-derived AOPs.Deeper mechanistic insight into their structure and function is expected to accelerate the development of novel peptide-based interventions for photoaging and other oxidative stress-associated dermatological disorders.展开更多
This study explores the broad-spectrum application of OsRALF26,a small secreted peptide belonging to the rapid alkalinization factor(RALF)family in rice.We found that the rice genome carries numerous lineage-specific ...This study explores the broad-spectrum application of OsRALF26,a small secreted peptide belonging to the rapid alkalinization factor(RALF)family in rice.We found that the rice genome carries numerous lineage-specific OsRALFs,suggesting that this evolutionary expansion could be the result of an arms race with pathogens.Among them,we focused on the Oryza-specific Os RALF26 and its closest homolog,OsRALF27,analyzing their effects across a range of plant species from monocots to dicots.The exogenous application of OsRALF26 significantly reduced bacterial populations in rice challenged with Xanthomonas oryzae pv.oryzae(Xoo)and in Arabidopsis and tomato challenged with Pseudomonas syringae pv.tomato DC3000(Pst DC3000),whereas Os RALF27 did not enhance resistance.展开更多
Umami peptides play important roles in the flavor of fermented broad bean paste(FBBP),and proteases produced by microorganisms contributed to the production of umami peptides.In order to reveal the formation of umami ...Umami peptides play important roles in the flavor of fermented broad bean paste(FBBP),and proteases produced by microorganisms contributed to the production of umami peptides.In order to reveal the formation of umami peptides and their relationships with protease-producing microorganisms during the natural fermentation of FBBP,peptidomics and virtual screening were used to identify and screen umami peptides.Meanwhile,macrogenomics was used to analyze the abundance of microbial-derived protease genes during FBBP fermentation.Then,based on the Pearson correlation coefficient,the correlation network diagram of each protease-producing microorganism with umami peptides was constructed.The results showed that a total of two exopeptidases and four endopeptidases were annotated from FBBP.Staphylococcus,Lactobacillus,Aspergillus,and Weissella can produce most proteases.The species Lactobacillus curvatus,Dyella jiangningensis,Erythrobacter sp.,and unclassified_g_Pantoea had strong correlation with umami peptides,and they may contribute to the process of protein hydrolysis to produce umami peptides.This study is expected to reveal the formation mechanism of umami peptides in FBBP,and the results of this study provided a better understanding of the relationship between proteases,microbiota,and core umami peptides in FBBP,which could help to improve the umami taste of Pixian Douban paste during fermentation.展开更多
Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In ...Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In this study,osteogenic growth peptide(OGP)and tetrahedral framework nucleic-acid nanostructures(tFNAs)are combined to form a peptide-DNA complex OGP-tFNAs,which aims to combine the positive biological effect on tissue protection and regeneration.The bone marrow protection and bone formation effect of OGP-tFNAs are investigated in chemotherapy-induced myelosuppressive mice.The results show that OGP-tFNAs could reduce the cell damage degree from 5-fluorouracil(5-FU)in vitro and maintained the osteogenic differentiation potential.Furthermore,OGP-tFNAs accelerate bone defect regeneration in myelosuppressive mice.In conclusion,OGP-tFNAs could protect the osteogenic differentiation potential of bone marrow stromal cells(BMSCs)from 5-FU injury and maintain the bone formation ability of myelosuppressive mice suffering from chemotherapy.展开更多
The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their bin...The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of 125I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically 125I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).展开更多
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
文摘Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).
基金supported by the National Natural Science Foundation of China(22378368).
文摘The blood-brain barrier(BBB)is a major challenge in drug delivery for the treatment of central nervous system diseases.Walnut derived peptide TWLPLPR(TW-7)has been proved to promote neuronal mitochondrial autophagy and enhance hippocampal neuronal synaptic plasticity,thereby improving learning and memory abilities in mice.We investigated the internalization mechanism and intracellular transport pathway for the walnut-derived peptide,TW-7,using b End.3 cells in an in vitro BBB model system.TW-7 was taken up by the b End.3 cells in a concentration-,temperature-,and energy-dependent manner;this involved increases in caveolin-1 and caveolin-2 protein expression and phosphorylation and inhibition of P-glycoprotein-mediated efflux.Subcellular localization of TW-7 in b End.3 cells was observed,indicating that the plasma membrane,endoplasmic reticulum,Golgi apparatus,lysosomes,and mitochondria participated in intracellular trafficking and that the peptide escaped from lysosomes over time.Caveolae may be critical for TW-7 uptake by brain microvascular endothelial cells,assisting TW-7 to cross the BBB.The results of this study provide a theoretical basis for the mechanism of active peptide penetrating the BBB,and provide a reference for developing neuroprotective active peptide products.
基金Financial support from the National Natural Science Foundation of China(32502106)One health Interdisciplinary Research Project,Institute of One Health Science,Ningbo University(NBUOH202502)the Ningbo Top Talent Project(215-432094250).
文摘The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.
基金supported by the National Natural Science Foundation of China(No.82104353)China Postdoctoral Science Foundation funded project(No.2022M711680).
文摘Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.
文摘Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications,with cardiovascular disease being a leading cause of mortality.Losing 5%-10%of body weight is considered clinically significant for improving health.This weight loss can be achieved through pharmacotherapy,including glucagon-like peptide 1(GLP-1)receptor agonists,GLP-1/glucosedependent insulinotropic peptide dual receptor agonists,and GLP-1/glucosedependent insulinotropic peptide/glucagon triple receptor agonists(such as semaglutide,tirzepatide,and retatrutide,respectively).While much of the weight loss comes from fat mass,these treatments also result in the loss of lean mass,including muscle.This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia.Therefore,the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass,ideally promoting muscle gain.Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction,which may play a crucial role in preserving both muscle mass and function.We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes.Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.
文摘Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy,which is often plagued by poor selectivity,off-target effects,and drug resistance.Among the various targeting agents in development,peptides stand out for their unique advantages,including minimal immunogenicity,high tissue penetration,and ease of modification.Their small size,specificity,and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively.Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery,improving tumor imaging,and reducing adverse effects.With cancer responsible for millions of deaths worldwide,the development of peptide-based therapeutics offers new hope in addressing the limitations of current treatments.As detailed studies on different aspects of targeting peptides are crucial for optimizing drug development,this review provides a comprehensive overview of the literature on tumor-targeting peptides,including their structure,sources,modes of action,and their application in cancer therapy—both as standalone agents and in fusion drugs.Additionally,various computational tools for peptide-based tumor-targeting drug design and validation are explored.The promising results from these studies highlight peptides as ideal candidates for targeted cancer therapies,offering valuable insights for researchers and accelerating the discovery of novel anti-tumor peptide base drug candidates.
文摘Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide combinations of the canonical residues has been previously reported.However,with increasing computational power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the complete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify potential small peptide inhibitors.
基金supported by the National Natural Science Foundation of China (Nos. 82173674 and 82204195)。
文摘Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.
基金supported by National Key Research and Development Program of China(Grant No.2021YFE0115200)the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(Grant No.U22A20356).
文摘Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.
文摘Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.
文摘Nine peptide-modified Salen-Co(Ⅱ)complexes based on three Salen ligand frameworks SA1~SA3 and four oligopeptides P1~P4 have been prepared.Their catalytic activities were examined through a model hydrohydrazination of cinnamic alcohol with azodicarboxylate.While peptide-modified Salen-Co(Ⅱ)complexes derived from SA1 are ineffective,its parent 1SalenCo and those based on SA2 and SA3 are excellent catalyst for this reaction.These results demonstrate that peptide ligands significantly modulate the catalytic activity of SalenCo(Ⅱ)complexes,particularly at lower temperatures,likely due to hydrogen-bonding interactions.
基金supported by the central government and guides local funds for science and technology development(2022ZY0109).
文摘The naturally fermented Inner Mongolian cheese’s flavor and nutritional value make it a popular choice among customers.In this work,to create multi-functional peptides that have taste and biological activity,peptidomics and bioinformatics were used to screen flavor peptides from Inner Mongolian cheese and further assess their antioxidant and angiotensin I-converting enzyme(ACE)inhibitory properties.According to sensory data,YH8 and IL7 had detectable bitter tastes with low thresholds of 0.03 and 0.06 mmol/L,respectively.With an umami threshold range of 0.24‒0.81 mmol/L,VQ6,FK13,HP13 and QT14 exhibited a range of flavors dominated by umami,including sweet,bitter,salty,sour and kokumi.Antioxidant activity wise,YH8,VQ6,HP13 and QT14 were well represented.The above-mentioned peptides all had some ACE inhibitory effect.The bitter peptide IL7(IC_(50)=0.08 mmol/L)had the highest level of ACE inhibitory activity,followed by YH8(IC_(50)=0.33 mmol/L).These multi-functional peptides,which have been assessed for bioactive and taste features in Inner Mongolian cheese,may have positive impacts on health and harmonize the cheese’s overall flavor.These results suggest that some flavor peptides produced in fermented foods might be with bioactivities while providing a basis for the exploration and application of multi-functional peptides.
基金funded by the National Natural Science Foundation of China(22478438,32401048,and 82273882)the Science Fund for Distinguished Young Scholars of Jiangsu Province(BK20240098)the Special Research Fund from the State Key Laboratory of Natural Medicines at China Pharmaceutical University(SKLNMZZ2024JS19).
文摘Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.
基金the financial support from the Zhejiang Provincial Natural Science Foundation of China(No.LBY24H040012)Discipline Cluster of Oncology of Wenzhou Medical University(No.z1-2023007)+1 种基金the financial support from the National Natural Science Foundation of China(No.32401107)the financial support from the Discipline Cluster of Oncology of Wenzhou Medical University(No.z3-2023027)。
文摘Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.
基金supported by the National Natural Science Foundation of China(32070439)Key Research&Development Plan in Social Development of Jiangsu Province(BE2022723)Suzhou Agricultural Science and Technology Innovation Project(SNG2022054)。
文摘Oxidative stress arises from disruption of the balance between reactive oxygen species(ROS)production and detoxification and constitutes a fundamental driver of diverse pathological diseases.Skin photoaging is a well-recognized example,primarily driven by chronic ultraviolet(UV)exposure and marked by progressive structural and functional deterioration.UV-induced ROS accelerate macromolecular degradation and impair epidermal and dermal barrier integrity,highlighting the urgent need for effective antioxidant interventions.Antioxidant peptides(AOPs),whether naturally occurring or synthetically engineered,have shown considerable potential in mitigating ROS-induced cellular damage.Amphibians,which possess highly permeable skin and are continuously challenged by fluctuating environmental conditions,represent a rich source of bioactive peptides with potent antioxidant properties.In particular,AOPs isolated from amphibian skin secretions demonstrate notable efficacy in ROS scavenging and mitigation of oxidative damage,offering promising candidates for anti-photoaging therapies.This review provides an integrated overview of ROS generation and signaling,the molecular mechanisms linking oxidative stress to skin photoaging,and the emerging biomedical potential of amphibian-derived AOPs.Deeper mechanistic insight into their structure and function is expected to accelerate the development of novel peptide-based interventions for photoaging and other oxidative stress-associated dermatological disorders.
基金supported by the National Research Foundation of Korea grant funded by the Korea government(Grant Nos.NRF-2020R1A2C1007778 and RS-2024-00454908)。
文摘This study explores the broad-spectrum application of OsRALF26,a small secreted peptide belonging to the rapid alkalinization factor(RALF)family in rice.We found that the rice genome carries numerous lineage-specific OsRALFs,suggesting that this evolutionary expansion could be the result of an arms race with pathogens.Among them,we focused on the Oryza-specific Os RALF26 and its closest homolog,OsRALF27,analyzing their effects across a range of plant species from monocots to dicots.The exogenous application of OsRALF26 significantly reduced bacterial populations in rice challenged with Xanthomonas oryzae pv.oryzae(Xoo)and in Arabidopsis and tomato challenged with Pseudomonas syringae pv.tomato DC3000(Pst DC3000),whereas Os RALF27 did not enhance resistance.
基金supported by the Science and Technology Department of Sichuan Province,China(2020YFN0151,23ZDYF3100)Chongqing Science and Technology Commission(cstc2021jscx-cylhX0014).
文摘Umami peptides play important roles in the flavor of fermented broad bean paste(FBBP),and proteases produced by microorganisms contributed to the production of umami peptides.In order to reveal the formation of umami peptides and their relationships with protease-producing microorganisms during the natural fermentation of FBBP,peptidomics and virtual screening were used to identify and screen umami peptides.Meanwhile,macrogenomics was used to analyze the abundance of microbial-derived protease genes during FBBP fermentation.Then,based on the Pearson correlation coefficient,the correlation network diagram of each protease-producing microorganism with umami peptides was constructed.The results showed that a total of two exopeptidases and four endopeptidases were annotated from FBBP.Staphylococcus,Lactobacillus,Aspergillus,and Weissella can produce most proteases.The species Lactobacillus curvatus,Dyella jiangningensis,Erythrobacter sp.,and unclassified_g_Pantoea had strong correlation with umami peptides,and they may contribute to the process of protein hydrolysis to produce umami peptides.This study is expected to reveal the formation mechanism of umami peptides in FBBP,and the results of this study provided a better understanding of the relationship between proteases,microbiota,and core umami peptides in FBBP,which could help to improve the umami taste of Pixian Douban paste during fermentation.
基金supported by National Natural Science Foundation of China(Nos.82322015,82171006)Sichuan Province Youth Science and Technology Innovation Team(No.2022JDTD0021)+3 种基金Sichuan Science and Technology Program(No.2022NSFSC0002)West China Hospital of Stomatology Sichuan University(No.RCDWJS2024-3)Sichuan Science and Technology Program(Nos.2023NSFSC1706,2024NSFSC1589)Postdoctoral Science Foundation of China(No.BX20220220)。
文摘Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In this study,osteogenic growth peptide(OGP)and tetrahedral framework nucleic-acid nanostructures(tFNAs)are combined to form a peptide-DNA complex OGP-tFNAs,which aims to combine the positive biological effect on tissue protection and regeneration.The bone marrow protection and bone formation effect of OGP-tFNAs are investigated in chemotherapy-induced myelosuppressive mice.The results show that OGP-tFNAs could reduce the cell damage degree from 5-fluorouracil(5-FU)in vitro and maintained the osteogenic differentiation potential.Furthermore,OGP-tFNAs accelerate bone defect regeneration in myelosuppressive mice.In conclusion,OGP-tFNAs could protect the osteogenic differentiation potential of bone marrow stromal cells(BMSCs)from 5-FU injury and maintain the bone formation ability of myelosuppressive mice suffering from chemotherapy.
基金Institutional support was provided by the project of the Czech Academy of Sciences,Czech Republic(to the Institute of Organic Chemistry and Biochemistry)(Project No.:RVO 61388963)This work was supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases(Programme EXCELES)funded by the European Union's Next Generation EU(Project No.:LX22NPO5104)the Czech Science Foundation,Czech Republic(Grant No.:23-05805S).
文摘The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of 125I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically 125I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).
