On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method...On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method for the synthesis of g-amino vinyl sulfonamides, key intermediates to the target molecules, was developed via the Wittig-Horner reaction of peptide aldehyde with Wittig reagents derived from methanesulfonamides.展开更多
AIM: To assess the clinical and economical validity of glutamine dipeptide supplemented to parenteral nutrition (PN) in patients undergoing abdominal surgery. METHODS: A meta-analysis of all the relevant randomized co...AIM: To assess the clinical and economical validity of glutamine dipeptide supplemented to parenteral nutrition (PN) in patients undergoing abdominal surgery. METHODS: A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. The trials compared the standard PN and PN supplemented with glutamine dipeptide in abdominal surgery. RCTs were identified from the following electronic databases: the Cochrane Library, MEDLINE, EMBASE and ISI web of knowledge (SCI). The search was undertaken in April 2006. Literature references were checked by computer or hand at the same time. Clinical trials were extracted and evaluated by two reviewers independently. Statistical analysis was performed by RevMan4.2 software from Cochrane Collaboration. A P value of < 0.05 was considered statistically significant. RESULTS: Nine RCTs involving 373 patients were included. The combined results showed that glutamine dipeptide has a positive effect in improving postoperative cumulative nitrogen balance (weighted mean difference (WMD = 8.35, 95% CI [2.98, 13.71], P = 0.002), decreasing postoperative infectious morbidity (OR = 0.24, 95% CI [0.06, 0.93], P = 0.04), shortening the length of hospital stay (WMD= -3.55, 95% CI [-5.26, -1.84], P < 0.00001). No serious adverse effects were found. CONCLUSION: Postoperative PN supplemented with glutamine dipeptide is effective and safe to decrease the infectious rate, reduce the length of hospital stay and improve nitrogen balance in patients undergoing abdominal surgery. Further high quality trials in children and severe patients are required, and mortality and hospital cost should be considered in future RCTs with sufficient size and rigorous design.展开更多
AIM： To investigate the protective effect and mechanism of alanyl-glutamine dipeptide （Ala-GIn） against hepatic ischemia-reperfusion injury in rats. METHODS： Rats were divided into group C as normal control Group ...AIM： To investigate the protective effect and mechanism of alanyl-glutamine dipeptide （Ala-GIn） against hepatic ischemia-reperfusion injury in rats. METHODS： Rats were divided into group C as normal control Group （/7=16） and group G as alanyl-glutamine pretreatment 07=16）. Rats were intravenously infused with 0.9% saline solution in group C and Ala-GIn -enriched （2% glutamine） 0.9% saline solution in group G via central venous catheter for three days. Then all rats underwent hepatic warm ischemia for 30 min followed by different periods of reperfusion. Changes in biochemical parameters, the content of glutathione （GSH） and the activity of superoxide dismutase （SOD） in liver tissue, Bcl-2 and Bax protein expression and morphological changes of liver tissue were compared between both groups. RESULTS： One hour after reperfusion, the levels of liver enzymes in group G were significantly lower than those in group C （P〈0.05）. Twenty-four hours after reperfusion, the levels of liver enzymes in both groups were markedly recovered and the levels of liver enzyme in group G were also significantly lower than those in group C （P〈0.01）. One and 24 h after reperfusion, GSH content in group G was significantly higher than that in group C （P 〈0.05）. There was no statistical difference in activities of SOD between the two groups. One and 24 h after reperfusion, the positive expression rate of Bcl-2 protein was higher in group G than in group C （P〈0.05） and the positive expression rate of Bax protein was lower in group G than in group C （P〈0.05）. Histological and ultrastructural changes of liver tissue were inhibited in group C compared to group G. CONCLUSION： Our results suggest that Ala-GIn pretreatment provides the rat liver with significant tolerance to warm ischemia-reperfusion injury, which may be mediated partially by enhancing GSH content and regulating the expression of Bcl-2 and Bax proteins in the liver tissue.展开更多
A simple and sensitive high performance liquid chromatography with fluorescence detection （HPLC-FD） has been developed for simultaneous quantification of doxorubicin （DOX） and its dipeptide conjugate prodrug （PDO...A simple and sensitive high performance liquid chromatography with fluorescence detection （HPLC-FD） has been developed for simultaneous quantification of doxorubicin （DOX） and its dipeptide conjugate prodrug （PDOX） in mice plasma. The chromatographic separation was carried out on an Amethyst C18-H column with gradient mobile phase of 0.1% formic acid and 0.1% formic acid in acetonitrile at a flow rate of 1.0 mL/min. The excitation and emission wavelengths were set at 490 and 550 nm, respectively. The method was comprehensively validated. The limits of detection were low up to 5.0 ng/mL for DOX and 25.0 ng/mL for PDOX. And the limits of quantification were low up to 12.5 ng/mL for DOX and 50 ng/mL for PDOX, which were lower than those for most of the current methods. The calibration curves showed good linearity （R2 〉 0.999） over the concentration ranges. The extraction recoveries ranged from 84.0% to 88.2% for DOX and from 85.4% to 89.2% for PDOX. Satisfactory intra-day and inter-day precisions were achieved with RSDs less than 9.1%. The results show that the developed HPLC-FD method is accurate, reliable and will be helpful for preclinical pharmacokinetic study of DOX and PDOX.展开更多
An experiment was conducted in a singly factorial design to study the effect of glycyl-glutamine dipeptide on enzyme activity, cell proliferation and apoptosis of jejunal tissues from weaned piglets at different glycy...An experiment was conducted in a singly factorial design to study the effect of glycyl-glutamine dipeptide on enzyme activity, cell proliferation and apoptosis of jejunal tissues from weaned piglets at different glycyl-glutamine concentration levels of 2, 4, 10, 20, and 30 mmol L-1, respectively. The glutaminase activity, diamine oxidase （DAO） activity, cell peoliferation, apoptosis, and perotein metabolism were measured by the tissue culture method in vitro using jejunal tissues. The immunohistochemical method was used to study the cell proliferation and apoptosis of jejunal tissues. The results showed that compared to the blank control, the percentage and MOD value of BrdU-positicve cells incubated with glycyl-glutamine dipeptide solution were significantly （P0.05） increased. Accordingly, the percentage and MOD value of caspase-3-positive cells from tissue incubated with glycyl-glutamine dipeptide were notably lower （P0.05） than that from the control treatment. The glycyl-glutamine dipeptide increased the glutaminase activity, DAO activity and protein content of jejunal tissues, as the dipeptide concentration was on the rise （P0.05）. These results indicated that glycyl-glutamine dipeptide affected the jejunum development and adaptation of weaned piglets, and the function might be fulfilled by enhancing the glutamine-related enzyme activity, thereby increasing the consumption of glutamine, and then improving the jejunal cell proliferation and suppressing cell apoptosis. The effects of glycyl-glutamine dipeptide relied in a dose-dependent manner, and the maximum effect was achieved at 20-30 mmol L-1 glycyl-glutamine dipeptide.展开更多
Cordyceps sinensis(C.sinensis)is a widely used and highly valuable traditional Chinese medicine.Several dipeptides have been detected in C.sinensis,but current scientific knowledge of its chemical makeup remains limit...Cordyceps sinensis(C.sinensis)is a widely used and highly valuable traditional Chinese medicine.Several dipeptides have been detected in C.sinensis,but current scientific knowledge of its chemical makeup remains limited.In this study,an improved approach that integrates offline two-dimensional liquid chromatography(2D LC)separation,precursor ion list,library screening,and diagnostic ion filtering was established to systematically screen and characterize dipeptides in C.sinensis.Offline 2D LC integrating hydrophilic interaction LC and reverse phase separations was established to eliminate interference and identify the target dipeptides.A library containing the potential 400 dipeptides was created,and a precursor ion list with all theoretical precursor ions was adopted to trigger the MS/MS scan with high sensitivity.To identify dipeptides,the type and connection sequence of amino acids were determined according to the product ions.Ile and Leu residues were differentiated for the first time according to the characteristic ion at m/z 69.07.Ultimately,170 dipeptides were identified or tentatively characterized from C.sinensis,and most are reported for the first time in this species herein.In addition,the identified dipeptides were also applied for discrimination among the three Cordyceps species,and 11 markers were identified.The obtained results provide a deeper understanding of the chemical basis of C.sinensis.展开更多
Peptide mimics derived with close structure to peptide have vast utility because they are expected to interfere with biological targets while having superior drug-like properties if compared to peptides. In this work,...Peptide mimics derived with close structure to peptide have vast utility because they are expected to interfere with biological targets while having superior drug-like properties if compared to peptides. In this work, novel vinyl dipeptides which are different in a double bond between the α-carbon of peptide and C1 of its side chain. Added to that, suitable substituents were selected to harness drug-like properties. The compounds were found to have moderate activities when tested against MCF-7 breast cancer cell line. For instance, the adamantyl analogue 2-(benzoylamino)-3-(2-furyl)-N-(1-adamantyl) propenamide (1c) and the heterocyclic analogue 2-(Benzoylamino)-3-(2-furyl)-N-[2-(5-cyanothia-zol-2-yl)] propenamide (1o) exhibited inhibition potency at 27.4 and 37.8 μM, respectively.展开更多
A method using N,O-bis（trimethylsilyl）acetamide/N-hydroxysuccinimide ester（BSA/NHS） as coupling agents for dipeptide synthesis is descried. The coupling reaction between N-hydroxysuccinimide（NHS）esters and amine...A method using N,O-bis（trimethylsilyl）acetamide/N-hydroxysuccinimide ester（BSA/NHS） as coupling agents for dipeptide synthesis is descried. The coupling reaction between N-hydroxysuccinimide（NHS）esters and amines could be performed under mild conditions with N,O-bis（trimethylsilyl）acetamide（BSA） as coupling reagent and no additional acid/base is required. All byproducts and excessive reactants are water soluble or hydrolysable and easy to eliminate through water-washing at the purification stage.Moreover, all the reactants are inexpensive and widely used in conventional drug production.展开更多
The development of small molecule nerve growth factor (NGF) mimetics is a promising approach to overcome limitations in the use of the neurotrophin as a drug, which are poor pharmacokinetics and undesirable side effec...The development of small molecule nerve growth factor (NGF) mimetics is a promising approach to overcome limitations in the use of the neurotrophin as a drug, which are poor pharmacokinetics and undesirable side effects. We designed dimeric dipeptide called GK-2 (bis(N-succinyl-L-glutamyl-L-lysine)hexametylendiamide) on the base of beta-turn sequence of NGF loop4 which most exposed to solvent and hence can play the major role in the interaction of NGF with the receptor. It was shown, that GK-2 stimulates phosphorylation of TrkA receptor, selectively activates PI3K/Akt signaling cascade that is important for cell survival, and does not activate MAPK/Erk pathway, associated not only with cell survival but also with cell differentiation. According to these data, GK-2 in vitro prevented H2O2- or MPTP- or glutamate-induced neuronal cell death at nanomolar concentrations, but did not provoke neurite outgrowth in PC12 cells. In vivo GK-2 exhibits therapeutic effects in models of Parkinson’s disease, Alzheimer’s disease, brain ischemia and diabetes mellitus. GK-2 shows activity in doses 0.01 - 5 mg/kg intraperitoneally and retains the activity after oral administration in dose 10 mg/kg. GK-2 has no side effects accompanying NGF treatment namely hyperalgesia and weight loss. Thus, the designed dimeric substituted dipeptide provides promising drug candidate and a molecular tool for investigating the possibility of divergence in NGF therapeutic and adverse effects.展开更多
For the first time, synthetic dipeptides were applied to the catalysis of asymmetric Reformatsky reaction. Review in this domain & factors influencing enantioselectivity were discussed.
As a non-specific modulator of macrophage, multiplied muramyl dipeptide (MMD) is solid-phase synthesized by application of standard Fmoc chemistry strategy. Tarn's multiple antigen system (MAS) is used as our four...As a non-specific modulator of macrophage, multiplied muramyl dipeptide (MMD) is solid-phase synthesized by application of standard Fmoc chemistry strategy. Tarn's multiple antigen system (MAS) is used as our four branched-linker on Lysine.展开更多
L-DOPA has gained widespread credit over the past decades as being the mainstay of the pharmacological treatment of Parkinson’s disease. However, there are many adverse effects associated with the use of L-DOPA. The ...L-DOPA has gained widespread credit over the past decades as being the mainstay of the pharmacological treatment of Parkinson’s disease. However, there are many adverse effects associated with the use of L-DOPA. The prodrug approach is the most promising way to solve the problem. In this article, a thionated dipeptide prodrug of L-DOPA 11 was synthesized via 10 steps in a total yield of 26.5% from L-DOPA.展开更多
Objective: To determine the active process on dipeptide transport with proton-and energy-dependence in Caco-2 cells.Methods: A human intestinal cell monolayer(Caco-2) was used as the in vitro model of human small inte...Objective: To determine the active process on dipeptide transport with proton-and energy-dependence in Caco-2 cells.Methods: A human intestinal cell monolayer(Caco-2) was used as the in vitro model of human small intestine and cephalexin as the model substrate for dipeptide transporter(PepT1).Caco-2 cells grown on multiwell dishes(24 wells) and Transwell membrane filters were incubated in the culture medium. The transport and uptake experiments of cephalexin across apical membranes were then conducted with different temperature and different pH values.Uptake of cephalexin in Caco-2 cells gsown on multiple well dishes with addition of energy inhibitors(sodium azide,SA and 2,4-dinitrophenol,DNP) were then measured. Results: The accumulation of cephalexin into Caco-2 monolayers increased with the duration of culture.The uptake from the apical surface was markedly influenced by the pH of the apical medium,and the maximal uptake was achieved at pH 5.5;further acidification of the incubation medium may decrease transport of cephalexin despite an increase inward H+ gradient.Cephalexin uptake was linear over the concentration range when the cells were incubated at 4℃ while the uptake rate was enhanced and tended to be saturated as the cephalexin concentration increased when the cells were incubated at 37℃.The kinetic parameters for the cephalexin transport carrier were determined to be: Vmax of(22.173±1.9) nmol/min per mg protein,Km of(2.069±0.9)mol/L,the Kd was estimated to be(0.07±0.02) nmol/min per mg protein per mmol/L.Uptake of cephalexin was markedly inhibited by sodium azide(SA) and 2,4-dinitrophenol(DNP). Conclusion: Cephalexin was transported actively across Caco-2 cells,and the transport process was proton-and energy-dependent.In addition, Caco-2 cells taked up cephalexin by dipeptide transporters that closely resembled the transporters present in the intestine.Caco-2 cells represented an ideal cellular model for future studies of the dipeptide transporter.展开更多
A new Schiff base (LK) obtained from 2, 4, -dihydroxybenzaldehyde and glycly-DL- phenylalanine reacted with Cu(II), Zn(II), Ni(II) and Co(II) to yield new complexes. The complexes were characterized by elemental an...A new Schiff base (LK) obtained from 2, 4, -dihydroxybenzaldehyde and glycly-DL- phenylalanine reacted with Cu(II), Zn(II), Ni(II) and Co(II) to yield new complexes. The complexes were characterized by elemental analyses, molar conductance, 1H NMR DTA, TG, IR and UV spectroscopy. In these complexes the ligand is coordinated to the metal through its phenolic oxygen, carboxyl oxygen, imino nitrogen and amide nitrogen. All complexes are non-electrolytes and four coordinated with 1:1(metal; ligand) stoichiometry. The probable structure of the complexes is suggested展开更多
The synthesis of dipeptide AcPheLeuNH2 catalyzed by immobilized pancreatic lipase was carried out in a two- liquid-phase hollow-fiber membrane reactor, operated in a batch mode. Kinetic properties of free and immobili...The synthesis of dipeptide AcPheLeuNH2 catalyzed by immobilized pancreatic lipase was carried out in a two- liquid-phase hollow-fiber membrane reactor, operated in a batch mode. Kinetic properties of free and immobilized enzyme, partition behavior between aqueous buffer phase and organic solvent phase, and effective diffusion coefficients of substrates and products through the membrane were investigated respectively. Based on the preliminary experimental results, the performance of the enzyme membrane reactor, which is evaluated by the purity and the yield, is discussed.展开更多
The solution-phase synthesis of a muramyl dipeptide（MDP） analogue of N~α-[4-chlorocinnamoyl-L-alanyl-D-isoglutaminyl]-L-lysine （MDA,2） is reported that possesses the features of easy feasibility,safety and low co...The solution-phase synthesis of a muramyl dipeptide（MDP） analogue of N~α-[4-chlorocinnamoyl-L-alanyl-D-isoglutaminyl]-L-lysine （MDA,2） is reported that possesses the features of easy feasibility,safety and low cost in large scale of synthesis.展开更多
Newlase F is a rude enzyme which contains triacylglycerol lipase and acid protease. Hydrolysis of dipeptide heptyl esters with Newlase F was studied in phosphate buffer-organic solvent by HPLC. When the Newlase F'...Newlase F is a rude enzyme which contains triacylglycerol lipase and acid protease. Hydrolysis of dipeptide heptyl esters with Newlase F was studied in phosphate buffer-organic solvent by HPLC. When the Newlase F's level reached 5 mg/mL under mild condition (PH 7.0, 30 degreesC), the lipase had the highest activity. The reaction was also affected greatly by organic solvents and their concentrations. It is found that protease in Newlase F does not hydrolyze amide bond under this condition (pH 7.0, r.t.).展开更多
A series of proline-based amino pyridine dipeptide organocatalysts was synthesized and applied in direct asymmetric intermolecular aldol reaction. These catalysts showed good solubility in organic solvents, good yiel...A series of proline-based amino pyridine dipeptide organocatalysts was synthesized and applied in direct asymmetric intermolecular aldol reaction. These catalysts showed good solubility in organic solvents, good yields （73%--97%） and enantioselectivitives（74%--94%）. Among them, dipeptide organocatalyst（2） was found to be the most efficient one for the asymmetric aldol reaction between cyclohexanone and 4-nitrobeznaldehyde. After optimizing the catalytic reaction conditions, we found that the catalyst showed high yield（97%）, enantioselectivity（e.e., up to 92%） and anti-diastcreoselectivity（up to 95：5） at mild room temperature without any additives.展开更多
基金Natural Science Foundation of China for the financial support(Grant No.30772626)
文摘On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method for the synthesis of g-amino vinyl sulfonamides, key intermediates to the target molecules, was developed via the Wittig-Horner reaction of peptide aldehyde with Wittig reagents derived from methanesulfonamides.
文摘AIM: To assess the clinical and economical validity of glutamine dipeptide supplemented to parenteral nutrition (PN) in patients undergoing abdominal surgery. METHODS: A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. The trials compared the standard PN and PN supplemented with glutamine dipeptide in abdominal surgery. RCTs were identified from the following electronic databases: the Cochrane Library, MEDLINE, EMBASE and ISI web of knowledge (SCI). The search was undertaken in April 2006. Literature references were checked by computer or hand at the same time. Clinical trials were extracted and evaluated by two reviewers independently. Statistical analysis was performed by RevMan4.2 software from Cochrane Collaboration. A P value of < 0.05 was considered statistically significant. RESULTS: Nine RCTs involving 373 patients were included. The combined results showed that glutamine dipeptide has a positive effect in improving postoperative cumulative nitrogen balance (weighted mean difference (WMD = 8.35, 95% CI [2.98, 13.71], P = 0.002), decreasing postoperative infectious morbidity (OR = 0.24, 95% CI [0.06, 0.93], P = 0.04), shortening the length of hospital stay (WMD= -3.55, 95% CI [-5.26, -1.84], P < 0.00001). No serious adverse effects were found. CONCLUSION: Postoperative PN supplemented with glutamine dipeptide is effective and safe to decrease the infectious rate, reduce the length of hospital stay and improve nitrogen balance in patients undergoing abdominal surgery. Further high quality trials in children and severe patients are required, and mortality and hospital cost should be considered in future RCTs with sufficient size and rigorous design.
基金Supported by the Natural Science Foundation of Liaoning Province, No. 20022063
文摘AIM： To investigate the protective effect and mechanism of alanyl-glutamine dipeptide （Ala-GIn） against hepatic ischemia-reperfusion injury in rats. METHODS： Rats were divided into group C as normal control Group （/7=16） and group G as alanyl-glutamine pretreatment 07=16）. Rats were intravenously infused with 0.9% saline solution in group C and Ala-GIn -enriched （2% glutamine） 0.9% saline solution in group G via central venous catheter for three days. Then all rats underwent hepatic warm ischemia for 30 min followed by different periods of reperfusion. Changes in biochemical parameters, the content of glutathione （GSH） and the activity of superoxide dismutase （SOD） in liver tissue, Bcl-2 and Bax protein expression and morphological changes of liver tissue were compared between both groups. RESULTS： One hour after reperfusion, the levels of liver enzymes in group G were significantly lower than those in group C （P〈0.05）. Twenty-four hours after reperfusion, the levels of liver enzymes in both groups were markedly recovered and the levels of liver enzyme in group G were also significantly lower than those in group C （P〈0.01）. One and 24 h after reperfusion, GSH content in group G was significantly higher than that in group C （P 〈0.05）. There was no statistical difference in activities of SOD between the two groups. One and 24 h after reperfusion, the positive expression rate of Bcl-2 protein was higher in group G than in group C （P〈0.05） and the positive expression rate of Bax protein was lower in group G than in group C （P〈0.05）. Histological and ultrastructural changes of liver tissue were inhibited in group C compared to group G. CONCLUSION： Our results suggest that Ala-GIn pretreatment provides the rat liver with significant tolerance to warm ischemia-reperfusion injury, which may be mediated partially by enhancing GSH content and regulating the expression of Bcl-2 and Bax proteins in the liver tissue.
基金supported by the National Natural Science Foundation of China (Grant nos. 21375101, 81573384 and 91417301)Natural Science Foundation of Hubei Province, China (No. 2014CFA077)Innovation Seed Fund and Translational Medical Research Fund of Wuhan University School of Medicine, China
文摘A simple and sensitive high performance liquid chromatography with fluorescence detection （HPLC-FD） has been developed for simultaneous quantification of doxorubicin （DOX） and its dipeptide conjugate prodrug （PDOX） in mice plasma. The chromatographic separation was carried out on an Amethyst C18-H column with gradient mobile phase of 0.1% formic acid and 0.1% formic acid in acetonitrile at a flow rate of 1.0 mL/min. The excitation and emission wavelengths were set at 490 and 550 nm, respectively. The method was comprehensively validated. The limits of detection were low up to 5.0 ng/mL for DOX and 25.0 ng/mL for PDOX. And the limits of quantification were low up to 12.5 ng/mL for DOX and 50 ng/mL for PDOX, which were lower than those for most of the current methods. The calibration curves showed good linearity （R2 〉 0.999） over the concentration ranges. The extraction recoveries ranged from 84.0% to 88.2% for DOX and from 85.4% to 89.2% for PDOX. Satisfactory intra-day and inter-day precisions were achieved with RSDs less than 9.1%. The results show that the developed HPLC-FD method is accurate, reliable and will be helpful for preclinical pharmacokinetic study of DOX and PDOX.
基金Sichuan Provincial Education Department of Outstanding Academic and Technical Youth Leadership Fund (2010JQ0043)the specific research supporting program for academic sustentation research team in Sichuan Agricultural University, China, for their financial supports
文摘An experiment was conducted in a singly factorial design to study the effect of glycyl-glutamine dipeptide on enzyme activity, cell proliferation and apoptosis of jejunal tissues from weaned piglets at different glycyl-glutamine concentration levels of 2, 4, 10, 20, and 30 mmol L-1, respectively. The glutaminase activity, diamine oxidase （DAO） activity, cell peoliferation, apoptosis, and perotein metabolism were measured by the tissue culture method in vitro using jejunal tissues. The immunohistochemical method was used to study the cell proliferation and apoptosis of jejunal tissues. The results showed that compared to the blank control, the percentage and MOD value of BrdU-positicve cells incubated with glycyl-glutamine dipeptide solution were significantly （P0.05） increased. Accordingly, the percentage and MOD value of caspase-3-positive cells from tissue incubated with glycyl-glutamine dipeptide were notably lower （P0.05） than that from the control treatment. The glycyl-glutamine dipeptide increased the glutaminase activity, DAO activity and protein content of jejunal tissues, as the dipeptide concentration was on the rise （P0.05）. These results indicated that glycyl-glutamine dipeptide affected the jejunum development and adaptation of weaned piglets, and the function might be fulfilled by enhancing the glutamine-related enzyme activity, thereby increasing the consumption of glutamine, and then improving the jejunal cell proliferation and suppressing cell apoptosis. The effects of glycyl-glutamine dipeptide relied in a dose-dependent manner, and the maximum effect was achieved at 20-30 mmol L-1 glycyl-glutamine dipeptide.
基金supported by the National Key R&D Program of China(Grant Nos.:2018YFC1707900,2019YFC1711000,and 2019YFC1711400)Key-Area Research and Development Program of Guangdong Province(Grant No.:2020B1111110007)+1 种基金the National Natural Science Foundation of China(Grant No.:82003938)Chief Scientist of Qi-Huang Project of National Traditional Chinese Medicine Inheritance and Innovation“One Hundred Million”Talent Project(2020).
文摘Cordyceps sinensis(C.sinensis)is a widely used and highly valuable traditional Chinese medicine.Several dipeptides have been detected in C.sinensis,but current scientific knowledge of its chemical makeup remains limited.In this study,an improved approach that integrates offline two-dimensional liquid chromatography(2D LC)separation,precursor ion list,library screening,and diagnostic ion filtering was established to systematically screen and characterize dipeptides in C.sinensis.Offline 2D LC integrating hydrophilic interaction LC and reverse phase separations was established to eliminate interference and identify the target dipeptides.A library containing the potential 400 dipeptides was created,and a precursor ion list with all theoretical precursor ions was adopted to trigger the MS/MS scan with high sensitivity.To identify dipeptides,the type and connection sequence of amino acids were determined according to the product ions.Ile and Leu residues were differentiated for the first time according to the characteristic ion at m/z 69.07.Ultimately,170 dipeptides were identified or tentatively characterized from C.sinensis,and most are reported for the first time in this species herein.In addition,the identified dipeptides were also applied for discrimination among the three Cordyceps species,and 11 markers were identified.The obtained results provide a deeper understanding of the chemical basis of C.sinensis.
文摘Peptide mimics derived with close structure to peptide have vast utility because they are expected to interfere with biological targets while having superior drug-like properties if compared to peptides. In this work, novel vinyl dipeptides which are different in a double bond between the α-carbon of peptide and C1 of its side chain. Added to that, suitable substituents were selected to harness drug-like properties. The compounds were found to have moderate activities when tested against MCF-7 breast cancer cell line. For instance, the adamantyl analogue 2-(benzoylamino)-3-(2-furyl)-N-(1-adamantyl) propenamide (1c) and the heterocyclic analogue 2-(Benzoylamino)-3-(2-furyl)-N-[2-(5-cyanothia-zol-2-yl)] propenamide (1o) exhibited inhibition potency at 27.4 and 37.8 μM, respectively.
基金financially supported by the National Science and Technology Major Project of China(No.521042)
文摘A method using N,O-bis（trimethylsilyl）acetamide/N-hydroxysuccinimide ester（BSA/NHS） as coupling agents for dipeptide synthesis is descried. The coupling reaction between N-hydroxysuccinimide（NHS）esters and amines could be performed under mild conditions with N,O-bis（trimethylsilyl）acetamide（BSA） as coupling reagent and no additional acid/base is required. All byproducts and excessive reactants are water soluble or hydrolysable and easy to eliminate through water-washing at the purification stage.Moreover, all the reactants are inexpensive and widely used in conventional drug production.
文摘The development of small molecule nerve growth factor (NGF) mimetics is a promising approach to overcome limitations in the use of the neurotrophin as a drug, which are poor pharmacokinetics and undesirable side effects. We designed dimeric dipeptide called GK-2 (bis(N-succinyl-L-glutamyl-L-lysine)hexametylendiamide) on the base of beta-turn sequence of NGF loop4 which most exposed to solvent and hence can play the major role in the interaction of NGF with the receptor. It was shown, that GK-2 stimulates phosphorylation of TrkA receptor, selectively activates PI3K/Akt signaling cascade that is important for cell survival, and does not activate MAPK/Erk pathway, associated not only with cell survival but also with cell differentiation. According to these data, GK-2 in vitro prevented H2O2- or MPTP- or glutamate-induced neuronal cell death at nanomolar concentrations, but did not provoke neurite outgrowth in PC12 cells. In vivo GK-2 exhibits therapeutic effects in models of Parkinson’s disease, Alzheimer’s disease, brain ischemia and diabetes mellitus. GK-2 shows activity in doses 0.01 - 5 mg/kg intraperitoneally and retains the activity after oral administration in dose 10 mg/kg. GK-2 has no side effects accompanying NGF treatment namely hyperalgesia and weight loss. Thus, the designed dimeric substituted dipeptide provides promising drug candidate and a molecular tool for investigating the possibility of divergence in NGF therapeutic and adverse effects.
文摘For the first time, synthetic dipeptides were applied to the catalysis of asymmetric Reformatsky reaction. Review in this domain & factors influencing enantioselectivity were discussed.
基金These studies were granted by the National Natural Science Foundation of China (39600183).
文摘As a non-specific modulator of macrophage, multiplied muramyl dipeptide (MMD) is solid-phase synthesized by application of standard Fmoc chemistry strategy. Tarn's multiple antigen system (MAS) is used as our four branched-linker on Lysine.
基金the National Natural Science Foundation of China(Project No.:30371681)Beijing Municipal Natural Science Foundation(Project No.:7042041)for the financial support
文摘L-DOPA has gained widespread credit over the past decades as being the mainstay of the pharmacological treatment of Parkinson’s disease. However, there are many adverse effects associated with the use of L-DOPA. The prodrug approach is the most promising way to solve the problem. In this article, a thionated dipeptide prodrug of L-DOPA 11 was synthesized via 10 steps in a total yield of 26.5% from L-DOPA.
基金The work was Supported by National Natural Science Foundation of China(30371392)
文摘Objective: To determine the active process on dipeptide transport with proton-and energy-dependence in Caco-2 cells.Methods: A human intestinal cell monolayer(Caco-2) was used as the in vitro model of human small intestine and cephalexin as the model substrate for dipeptide transporter(PepT1).Caco-2 cells grown on multiwell dishes(24 wells) and Transwell membrane filters were incubated in the culture medium. The transport and uptake experiments of cephalexin across apical membranes were then conducted with different temperature and different pH values.Uptake of cephalexin in Caco-2 cells gsown on multiple well dishes with addition of energy inhibitors(sodium azide,SA and 2,4-dinitrophenol,DNP) were then measured. Results: The accumulation of cephalexin into Caco-2 monolayers increased with the duration of culture.The uptake from the apical surface was markedly influenced by the pH of the apical medium,and the maximal uptake was achieved at pH 5.5;further acidification of the incubation medium may decrease transport of cephalexin despite an increase inward H+ gradient.Cephalexin uptake was linear over the concentration range when the cells were incubated at 4℃ while the uptake rate was enhanced and tended to be saturated as the cephalexin concentration increased when the cells were incubated at 37℃.The kinetic parameters for the cephalexin transport carrier were determined to be: Vmax of(22.173±1.9) nmol/min per mg protein,Km of(2.069±0.9)mol/L,the Kd was estimated to be(0.07±0.02) nmol/min per mg protein per mmol/L.Uptake of cephalexin was markedly inhibited by sodium azide(SA) and 2,4-dinitrophenol(DNP). Conclusion: Cephalexin was transported actively across Caco-2 cells,and the transport process was proton-and energy-dependent.In addition, Caco-2 cells taked up cephalexin by dipeptide transporters that closely resembled the transporters present in the intestine.Caco-2 cells represented an ideal cellular model for future studies of the dipeptide transporter.
文摘A new Schiff base (LK) obtained from 2, 4, -dihydroxybenzaldehyde and glycly-DL- phenylalanine reacted with Cu(II), Zn(II), Ni(II) and Co(II) to yield new complexes. The complexes were characterized by elemental analyses, molar conductance, 1H NMR DTA, TG, IR and UV spectroscopy. In these complexes the ligand is coordinated to the metal through its phenolic oxygen, carboxyl oxygen, imino nitrogen and amide nitrogen. All complexes are non-electrolytes and four coordinated with 1:1(metal; ligand) stoichiometry. The probable structure of the complexes is suggested
基金Supported by the National Natural Science Foundation of China andExtraction Separation branch of United Chemical Engineeing
文摘The synthesis of dipeptide AcPheLeuNH2 catalyzed by immobilized pancreatic lipase was carried out in a two- liquid-phase hollow-fiber membrane reactor, operated in a batch mode. Kinetic properties of free and immobilized enzyme, partition behavior between aqueous buffer phase and organic solvent phase, and effective diffusion coefficients of substrates and products through the membrane were investigated respectively. Based on the preliminary experimental results, the performance of the enzyme membrane reactor, which is evaluated by the purity and the yield, is discussed.
基金supported financially by the National Natural Science Foundation of China(No.90713045)
文摘The solution-phase synthesis of a muramyl dipeptide（MDP） analogue of N~α-[4-chlorocinnamoyl-L-alanyl-D-isoglutaminyl]-L-lysine （MDA,2） is reported that possesses the features of easy feasibility,safety and low cost in large scale of synthesis.
文摘Newlase F is a rude enzyme which contains triacylglycerol lipase and acid protease. Hydrolysis of dipeptide heptyl esters with Newlase F was studied in phosphate buffer-organic solvent by HPLC. When the Newlase F's level reached 5 mg/mL under mild condition (PH 7.0, 30 degreesC), the lipase had the highest activity. The reaction was also affected greatly by organic solvents and their concentrations. It is found that protease in Newlase F does not hydrolyze amide bond under this condition (pH 7.0, r.t.).
基金Supported by the National Natural Science Foundation of China(Nos.20802025 and 20082011)
文摘A series of proline-based amino pyridine dipeptide organocatalysts was synthesized and applied in direct asymmetric intermolecular aldol reaction. These catalysts showed good solubility in organic solvents, good yields （73%--97%） and enantioselectivitives（74%--94%）. Among them, dipeptide organocatalyst（2） was found to be the most efficient one for the asymmetric aldol reaction between cyclohexanone and 4-nitrobeznaldehyde. After optimizing the catalytic reaction conditions, we found that the catalyst showed high yield（97%）, enantioselectivity（e.e., up to 92%） and anti-diastcreoselectivity（up to 95：5） at mild room temperature without any additives.
