美洲鳄梨变种防御素(Persea americana var. drymifolia defensin,PaDef)是从墨西哥鳄梨果实中提取的一种具有广谱抗菌作用的防御素,其结构-活性构效关系及其抗菌机制尚未明确。该文利用定点突变的方法对重组PaDef(recombination PaDef,...美洲鳄梨变种防御素(Persea americana var. drymifolia defensin,PaDef)是从墨西哥鳄梨果实中提取的一种具有广谱抗菌作用的防御素,其结构-活性构效关系及其抗菌机制尚未明确。该文利用定点突变的方法对重组PaDef(recombination PaDef,rPaDef)进行定向分子改良。最终获得改良肽rPaDefQ33H和rPaDefK43M,其抗菌活性上调2~3倍,同时保持良好的稳定性和较低的溶血性和细胞毒性。用扫描电子显微镜和荧光显微探究rPaDef及改良肽的抗菌机制,表明rPaDef及改良肽能够在细菌表面产生孔隙,破坏受试菌的细胞完整性,最终导致细菌死亡。因此rPaDef及改良肽可以作为新型抗生素替代物,在食品贮藏保鲜、绿色饲料添加剂以及临床医药领域等方面有较大应用前景。展开更多
Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sh...Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sheets rely on such interactions for stability,limiting control over exposed interacting moieties.Here,we reported a novel,frame-like peptide scaffold that maintains exceptional stability without intramolecular interactions.This structure exposes its backbone and orients side chains for hierarchical self-assembly into micron-scale cubes.By introducing mutations at specific sites,we controlled packing orientations,offering new options for tunable self-assembly.Our scaffold provides a versatile platform for designing advanced peptide materials,with applications in nanotechnology and biomaterials.展开更多
Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptid...Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptides with potent anti-proliferative activities against cancer cells,through C-H alkenylation and macrolactamization.This report addresses critical challenges associated with the installation and removal of the directing group N-Piv,configuration selectivity of the olefin,and intramolecular cyclization.No-tably,this method exhibits mild reaction conditions,traceless removal of the directing group,and high configuration selectivity.展开更多
Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine...Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine,O-methylthreonine,hexahydropyridazine-3-carboxylic acid,5-hydroxytetrahydropyridazine-3-carboxylic acid,and(2S,3R,4E,6E)-2-amino-3–hydroxy-4,6-dienoic acid residues.Pyridapeptide I(4)contains(2S,3R,4E,6E)-2-amino-3–hydroxy-8-methylnona-4,6-dienoic acid residue and a very rare glycose residue,aculose.Their structures were determined based on spectroscopic analysis and chemical methods.Pyridapeptides G–I(2–4)have the 2,3,6-trideoxyhexose units glycosylated at theγ-OH-TPDA residue,displayed significant antiproliferative activity against four(PC9,MKN45,Hep G2,K562)or two(PC9,MKN45)human cancer cell lines.展开更多
HIGHLIGHTS The formation of peptide nanocapsules is facilitated by a gradient interface,where the differential solvent concentration drives the peptides to preferentially localize and assemble.The peptide nanocapsules...HIGHLIGHTS The formation of peptide nanocapsules is facilitated by a gradient interface,where the differential solvent concentration drives the peptides to preferentially localize and assemble.The peptide nanocapsules,characterized by their hollow structures,demonstrated potential as carriers for targeted drug delivery.1 Introduction Peptide nanocapsules are a type of nanoscale delivery system that encapsulates active substances within a shell composed of peptides,leveraging the unique properties of peptides such as biocompatibility and biodegradability[1].Historically,the development of peptide nanocapsules was inspired primordially by the natural biological processes.展开更多
文摘美洲鳄梨变种防御素(Persea americana var. drymifolia defensin,PaDef)是从墨西哥鳄梨果实中提取的一种具有广谱抗菌作用的防御素,其结构-活性构效关系及其抗菌机制尚未明确。该文利用定点突变的方法对重组PaDef(recombination PaDef,rPaDef)进行定向分子改良。最终获得改良肽rPaDefQ33H和rPaDefK43M,其抗菌活性上调2~3倍,同时保持良好的稳定性和较低的溶血性和细胞毒性。用扫描电子显微镜和荧光显微探究rPaDef及改良肽的抗菌机制,表明rPaDef及改良肽能够在细菌表面产生孔隙,破坏受试菌的细胞完整性,最终导致细菌死亡。因此rPaDef及改良肽可以作为新型抗生素替代物,在食品贮藏保鲜、绿色饲料添加剂以及临床医药领域等方面有较大应用前景。
基金supported by the National Basic Research Program of China 973 Program(Nos.2021YFA0910803,2021YFC2103900)the National Natural Science Foundation of China(No.21977011)+4 种基金the Natural Science Foundation of Guangdong Province(Nos.2022A1515010996 and 2020A1515011544)the Shenzhen Science and Technology Innovation Committee(Nos.RCJC20200714114433053,JCYJ20180507181527112 and JCYJ20200109140406047)the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(No.2019SHIBS0004)the Shenzhen Fundamental Research Program(No.GXWD20201231165807007–20200827170132001)Tian Fu Jin Cheng Laboratory(Advanced Medical Center)Group Racing Project(No.TFJC2023010008)。
文摘Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sheets rely on such interactions for stability,limiting control over exposed interacting moieties.Here,we reported a novel,frame-like peptide scaffold that maintains exceptional stability without intramolecular interactions.This structure exposes its backbone and orients side chains for hierarchical self-assembly into micron-scale cubes.By introducing mutations at specific sites,we controlled packing orientations,offering new options for tunable self-assembly.Our scaffold provides a versatile platform for designing advanced peptide materials,with applications in nanotechnology and biomaterials.
基金the National Key R&D Program of China(No.2022YFA1302900 to H.Liu)National Natural Science Foundation of China(Nos.82130105,22337003,82121005 to H.Liu+2 种基金and Nos.22177124,82322063 to J.Wang)Program of Shang-hai Academic Research Leader(No.23XD1460300 to J.Wang)the Lingang Laboratory(No.LG-GG-202204-02 to J.Wang)for supporting this work.We would like to acknowledge Shanghai Highline Therapeutics.
文摘Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptides with potent anti-proliferative activities against cancer cells,through C-H alkenylation and macrolactamization.This report addresses critical challenges associated with the installation and removal of the directing group N-Piv,configuration selectivity of the olefin,and intramolecular cyclization.No-tably,this method exhibits mild reaction conditions,traceless removal of the directing group,and high configuration selectivity.
基金financially supported by the National Natural Science Foundation of China(No.U1906213)the National Key Research and Development Program of China(No.2022YFC2804100)。
文摘Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine,O-methylthreonine,hexahydropyridazine-3-carboxylic acid,5-hydroxytetrahydropyridazine-3-carboxylic acid,and(2S,3R,4E,6E)-2-amino-3–hydroxy-4,6-dienoic acid residues.Pyridapeptide I(4)contains(2S,3R,4E,6E)-2-amino-3–hydroxy-8-methylnona-4,6-dienoic acid residue and a very rare glycose residue,aculose.Their structures were determined based on spectroscopic analysis and chemical methods.Pyridapeptides G–I(2–4)have the 2,3,6-trideoxyhexose units glycosylated at theγ-OH-TPDA residue,displayed significant antiproliferative activity against four(PC9,MKN45,Hep G2,K562)or two(PC9,MKN45)human cancer cell lines.
文摘HIGHLIGHTS The formation of peptide nanocapsules is facilitated by a gradient interface,where the differential solvent concentration drives the peptides to preferentially localize and assemble.The peptide nanocapsules,characterized by their hollow structures,demonstrated potential as carriers for targeted drug delivery.1 Introduction Peptide nanocapsules are a type of nanoscale delivery system that encapsulates active substances within a shell composed of peptides,leveraging the unique properties of peptides such as biocompatibility and biodegradability[1].Historically,the development of peptide nanocapsules was inspired primordially by the natural biological processes.
