Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.Both rheumatoid factor and anti-cyclic citrullinated peptide antibodies positive psoriatic arthritis patients may be in risk for development o...Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.Both rheumatoid factor and anti-cyclic citrullinated peptide antibodies positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Symmetrical polyarthritis pattern was predominant(42%)among clinical pattern of psoriatic arthritis.Among 10 rheumatoid factor positive patients,8(80%)patients had symmetrical polyarthritis pattern and out of 7 anti-cyclic citrullinated peptide antibody positive patients,7(100%)patients had symmetrical polyarthritis pattern.Association of anti-cyclic citrullinated peptide(P=0.008)and rheumatoid factor(P=0.006)showed statistical significance with symmetrical polyarthritis pattern.Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Background:Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.It is usually seronegative in nature but a small percentage of patients may be positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Anti-cyclic citrullinated peptide and rheumatoid factor are highly specific for rheumatoid arthritis but their role is not clear in psoriatic arthritis.The prevalence and prognostic value of anti-cyclic citrullinated peptide antibody and rheumatoid factor in psoriatic arthritis patients is not well known.The aim of this study was therefore to investigate the prevalence of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in psoriatic arthritis patients and assess their clinical associations and also to see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Methods:Fifty patients with psoriatic arthritis were tested for the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Polymerase chain reaction was done with sequence specific primer for detection of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Data on five clinical patterns of rheumatological manifestations of psoriatic arthritis patients were collected prospectively on all patients and statistically compared between anti-cyclic citrullinated peptide,rheumatoid factor positive and negative patients by chi-square test.We also see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Results:Among 50 psoriatic arthritis patients,rheumatoid arthritis test was positive in 10(20%)patients and anti-cyclic citrullinated peptide was positive in 7(14%)patients.Symmetrical polyarthritis pattern is predominant among clinical pattern of psoriatic arthritis which was found in 21(42%)patients.Among 7 anti-cyclic citrullinated peptide positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 7(100%)patients.Among 10 rheumatoid factor positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 8(80%)patients.In this study,symmetrical polyarthritis pattern is statistically associated with anti-cyclic citrullinated peptide positive psoriatic arthritis patients(P=0.008)and rheumatoid factor positive psoriatic arthritis patients(P=0.006).Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Conclusion:Both rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Among rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients,Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 alleles were more frequently found alleles.展开更多
Background:Clinical outcomes of undifferentiated arthritis(UA)are diverse,and only 40%of patients with UA develop rheumatoid arthritis(RA)after 3 years.Discovering predictive markers at disease onset for further inter...Background:Clinical outcomes of undifferentiated arthritis(UA)are diverse,and only 40%of patients with UA develop rheumatoid arthritis(RA)after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17(7.3%)patients failed to follow up during the study.Among the 217 patients who completed the study,83(38.2%)patients went into remission.UA patients who developed RA had a higher rheumatoid factor(RF)-positivity(42.9%vs.16.8%,χ^2=8.228,P=0.008),anti-cyclic citrullinated peptide(CCP)antibodypositivity(66.7%vs.10.7%,χ^2=43.897,P<0.001),and double-positivity rate of RF and anti-CCP antibody(38.1%vs.4.1%,χ^2=32.131,P<0.001)than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development(hazard ratio 18.017,95%confidence interval:5.803–55.938;P<0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.展开更多
From Psammosilene tunicoides W. C. Wu et C. Y Wu, two cyclic octapeptides (namedpsammosilenins A and B) were isolated. Their structures were determined as cyclo(-Pro1-phe1-Pro2-Phe2-Phe3-Ala-Pro3-Leu-) and cyclo(-Pro1...From Psammosilene tunicoides W. C. Wu et C. Y Wu, two cyclic octapeptides (namedpsammosilenins A and B) were isolated. Their structures were determined as cyclo(-Pro1-phe1-Pro2-Phe2-Phe3-Ala-Pro3-Leu-) and cyclo(-Pro1-Gly-Phe1-Val-Pro2-Phe2-Thr-Ile) by spectroscopicmethods.展开更多
A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The l...A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilizat...展开更多
Using Au6 cluster and cyclooctaglycine model for gold nanoparticle(AuNP) and cyclic peptide(CP), twelve configurations for the functionalization of cyclic peptide-gold nanoparticle(CPAuNP) with gemcitabine(GEM) antica...Using Au6 cluster and cyclooctaglycine model for gold nanoparticle(AuNP) and cyclic peptide(CP), twelve configurations for the functionalization of cyclic peptide-gold nanoparticle(CPAuNP) with gemcitabine(GEM) anticancer drug were investigated(CPAuNP/GEM1-12). Structural and electronic properties have been studied in gas phase and aqueous solution at M06-2 X/6-31 g(d,p). The energetic stability of CPAuNP/GEM1-12 was confirmed by the calculation of binding energies. Since the solubility of drug, CP and AuNP increases in CPAuNP/GEM1-12, cyclic peptide-gold nanoparticle could be used as an appropriate drug delivery system. Quantum molecular descriptors such as electrophilicity power and global hardness demonstrated that the reactivity of CP and GEM drug increases in CPAuNP/GEM1-12 configurations. The AIM analysis for CPAuNP/GEM1-12 indicated that the Au-L(L = H, O, F, C, N) interactions and intermolecular hydrogen bonds play important roles in this drug delivery system. All Au-Au and some of Au-L interactions are related to medium interactions. The most stable configurations are those in which GEM drug is parallel to the CPAuNP and interacts simultaneously with AuNP and CP.展开更多
New cyclic peptides 1 and 2 were isolated from the endophytic fungus #2221 fromCastaniopsis fissa on the south China sea coast. By 2D NMR methods and chiral HPLC technique,their structures were elucidated as cyclo (L-...New cyclic peptides 1 and 2 were isolated from the endophytic fungus #2221 fromCastaniopsis fissa on the south China sea coast. By 2D NMR methods and chiral HPLC technique,their structures were elucidated as cyclo (L-Val-L-Leu-L-Val-L-Leu) and cyclo(L-Leu-L-Ala-L-Leu-L-Ala), respectively.展开更多
Background and objective Metastasis is one of the most important causes of mortality in tumor. The pathological process of metastasis includes several sequential steps as
Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigid...Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigidity.However,cyclic peptides could form numerous putative metabolites from potential hydrolytic cleavages and their fragments are very difficult to interpret.These characteristics pose a great challenge when analyzing metabolites of cyclic peptides by mass spectrometry.This study was to assess and apply a software-aided analytical workflow for the detection and structural characterization of cyclic peptide metabolites.Insulin and atrial natriuretic peptide(ANP)as model cyclic peptides were incubated with trypsin/chymotrypsin and/or rat liver S9,followed by data acquisition using TripleTOF?5600.Resultant full-scan MS and MS/MS datasets were automatically processed through a combination of targeted and untargeted peak finding strategies.MS/MS spectra of predicted metabolites were interrogated against putative metabolite sequences,in light of a,b,y and internal fragment series.The resulting fragment assignments led to the confirmation and ranking of the metabolite sequences and identification of metabolic modification.As a result,29 metabolites with linear or cyclic structures were detected in the insulin incubation with the hydrolytic enzymes.Sequences of twenty insulin metabolites were further determined,which were consistent with the hydrolytic sites of these enzymes.In the same manner,multiple metabolites of insulin and ANP formed in rat liver S9 incubation were detected and structurally characterized,some of which have not been previously reported.The results demonstrated the utility of software-aided data processing tool in detection and identification of cyclic peptide metabolites.展开更多
A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our 揗eshed-Bag Gathered-Bunch?method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl2,6-dioxocyc...A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our 揗eshed-Bag Gathered-Bunch?method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl2,6-dioxocyclo-hexylidene)ethyl chemical protection strategy.展开更多
The Antarctic fungus Cadophora malorum produces previously undescribed cyclic heptapeptides(cadophorin A and B)containing an anthranilic acid residue.The planar structure of these peptides was determined by high-resol...The Antarctic fungus Cadophora malorum produces previously undescribed cyclic heptapeptides(cadophorin A and B)containing an anthranilic acid residue.The planar structure of these peptides was determined by high-resolution mass spectrometry combined with extensive 1D and 2D NMR spectroscopy.The absolute configuration of the amino acids was determined by Marfey’s method,with HPLC analysis of FDVA(Nα-(2,4-dinitro-5-fluorphenyl)-l-valinamide)derivatives making use of a PFP column.Remarkably,cadophorin 2 possesses both the uncommon d-Ile and d-allo-Ile in its structure.The peptides have metal binding properties as shown by LCMS with post column addition of metal salt solutions.These results were supported by DFT calculations.展开更多
A highly hydrophobic cyclic peptide GG-110824,cyclo(Gly-Leu-Val-Leu-LeuVal-Pro-Ile-Gly-Leu)(C49H86N10O10),has been synthesized by a strategy combined with solid-phase synthesis(SPPS) of linear peptide and cyclization ...A highly hydrophobic cyclic peptide GG-110824,cyclo(Gly-Leu-Val-Leu-LeuVal-Pro-Ile-Gly-Leu)(C49H86N10O10),has been synthesized by a strategy combined with solid-phase synthesis(SPPS) of linear peptide and cyclization in solution.The structure including the absolute configuration of synthesized GG-110824 was confirmed by CuK radiation X-ray crystallography in the monoclinic system,space group P21 with a = 11.4966(10),b = 18.5286(2),c = 13.3943(10),= 95.03o,V = 2842.20(4)3,F(000) = 1080 and Z = 2.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
文摘Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.Both rheumatoid factor and anti-cyclic citrullinated peptide antibodies positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Symmetrical polyarthritis pattern was predominant(42%)among clinical pattern of psoriatic arthritis.Among 10 rheumatoid factor positive patients,8(80%)patients had symmetrical polyarthritis pattern and out of 7 anti-cyclic citrullinated peptide antibody positive patients,7(100%)patients had symmetrical polyarthritis pattern.Association of anti-cyclic citrullinated peptide(P=0.008)and rheumatoid factor(P=0.006)showed statistical significance with symmetrical polyarthritis pattern.Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Background:Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.It is usually seronegative in nature but a small percentage of patients may be positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Anti-cyclic citrullinated peptide and rheumatoid factor are highly specific for rheumatoid arthritis but their role is not clear in psoriatic arthritis.The prevalence and prognostic value of anti-cyclic citrullinated peptide antibody and rheumatoid factor in psoriatic arthritis patients is not well known.The aim of this study was therefore to investigate the prevalence of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in psoriatic arthritis patients and assess their clinical associations and also to see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Methods:Fifty patients with psoriatic arthritis were tested for the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Polymerase chain reaction was done with sequence specific primer for detection of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Data on five clinical patterns of rheumatological manifestations of psoriatic arthritis patients were collected prospectively on all patients and statistically compared between anti-cyclic citrullinated peptide,rheumatoid factor positive and negative patients by chi-square test.We also see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Results:Among 50 psoriatic arthritis patients,rheumatoid arthritis test was positive in 10(20%)patients and anti-cyclic citrullinated peptide was positive in 7(14%)patients.Symmetrical polyarthritis pattern is predominant among clinical pattern of psoriatic arthritis which was found in 21(42%)patients.Among 7 anti-cyclic citrullinated peptide positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 7(100%)patients.Among 10 rheumatoid factor positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 8(80%)patients.In this study,symmetrical polyarthritis pattern is statistically associated with anti-cyclic citrullinated peptide positive psoriatic arthritis patients(P=0.008)and rheumatoid factor positive psoriatic arthritis patients(P=0.006).Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Conclusion:Both rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Among rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients,Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 alleles were more frequently found alleles.
基金The study was supported by the grants from the Ministry of Science and Technology of China(No.2008BAI59800 and 2014BAI07B01)the National Natural Science Foundation of China(No.81671609)Beijing Municipal Science and Technology Project(No.Z171100000417007).
文摘Background:Clinical outcomes of undifferentiated arthritis(UA)are diverse,and only 40%of patients with UA develop rheumatoid arthritis(RA)after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17(7.3%)patients failed to follow up during the study.Among the 217 patients who completed the study,83(38.2%)patients went into remission.UA patients who developed RA had a higher rheumatoid factor(RF)-positivity(42.9%vs.16.8%,χ^2=8.228,P=0.008),anti-cyclic citrullinated peptide(CCP)antibodypositivity(66.7%vs.10.7%,χ^2=43.897,P<0.001),and double-positivity rate of RF and anti-CCP antibody(38.1%vs.4.1%,χ^2=32.131,P<0.001)than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development(hazard ratio 18.017,95%confidence interval:5.803–55.938;P<0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.
文摘From Psammosilene tunicoides W. C. Wu et C. Y Wu, two cyclic octapeptides (namedpsammosilenins A and B) were isolated. Their structures were determined as cyclo(-Pro1-phe1-Pro2-Phe2-Phe3-Ala-Pro3-Leu-) and cyclo(-Pro1-Gly-Phe1-Val-Pro2-Phe2-Thr-Ile) by spectroscopicmethods.
基金supported by National Natural Science Foundation(No.30672546)Shanghai Municipal Committee of S & T(No.0652nm013)National Key Basic Research Program of China(No.2007CB935800)
文摘A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilizat...
文摘Using Au6 cluster and cyclooctaglycine model for gold nanoparticle(AuNP) and cyclic peptide(CP), twelve configurations for the functionalization of cyclic peptide-gold nanoparticle(CPAuNP) with gemcitabine(GEM) anticancer drug were investigated(CPAuNP/GEM1-12). Structural and electronic properties have been studied in gas phase and aqueous solution at M06-2 X/6-31 g(d,p). The energetic stability of CPAuNP/GEM1-12 was confirmed by the calculation of binding energies. Since the solubility of drug, CP and AuNP increases in CPAuNP/GEM1-12, cyclic peptide-gold nanoparticle could be used as an appropriate drug delivery system. Quantum molecular descriptors such as electrophilicity power and global hardness demonstrated that the reactivity of CP and GEM drug increases in CPAuNP/GEM1-12 configurations. The AIM analysis for CPAuNP/GEM1-12 indicated that the Au-L(L = H, O, F, C, N) interactions and intermolecular hydrogen bonds play important roles in this drug delivery system. All Au-Au and some of Au-L interactions are related to medium interactions. The most stable configurations are those in which GEM drug is parallel to the CPAuNP and interacts simultaneously with AuNP and CP.
基金This work was supported by the National Natural Science Foundation of China(0072058)863 Foundation of China(2003AA624010)+2 种基金the National Natural Science Foundation of Guangdong Province,China(021732,2003A 3050401)a strategic grant at City University of Hong Kong(7000650)E.B.G.J.acknowledges the Royal Society,U.K.and City University of Hong Kong for the award of the Kan Tong Po Visiting Professorship.
文摘New cyclic peptides 1 and 2 were isolated from the endophytic fungus #2221 fromCastaniopsis fissa on the south China sea coast. By 2D NMR methods and chiral HPLC technique,their structures were elucidated as cyclo (L-Val-L-Leu-L-Val-L-Leu) and cyclo(L-Leu-L-Ala-L-Leu-L-Ala), respectively.
基金supported partially by Natural Science Foundation of Shandong Province (Y2005D14)Science and Technology Program of Yantai City (2008152)the Scientic Research Foundation from Education Ministry for the Returned Overseas Chinese Scholars and the Scientic Research Foundation of Ludong University
文摘Background and objective Metastasis is one of the most important causes of mortality in tumor. The pathological process of metastasis includes several sequential steps as
文摘Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigidity.However,cyclic peptides could form numerous putative metabolites from potential hydrolytic cleavages and their fragments are very difficult to interpret.These characteristics pose a great challenge when analyzing metabolites of cyclic peptides by mass spectrometry.This study was to assess and apply a software-aided analytical workflow for the detection and structural characterization of cyclic peptide metabolites.Insulin and atrial natriuretic peptide(ANP)as model cyclic peptides were incubated with trypsin/chymotrypsin and/or rat liver S9,followed by data acquisition using TripleTOF?5600.Resultant full-scan MS and MS/MS datasets were automatically processed through a combination of targeted and untargeted peak finding strategies.MS/MS spectra of predicted metabolites were interrogated against putative metabolite sequences,in light of a,b,y and internal fragment series.The resulting fragment assignments led to the confirmation and ranking of the metabolite sequences and identification of metabolic modification.As a result,29 metabolites with linear or cyclic structures were detected in the insulin incubation with the hydrolytic enzymes.Sequences of twenty insulin metabolites were further determined,which were consistent with the hydrolytic sites of these enzymes.In the same manner,multiple metabolites of insulin and ANP formed in rat liver S9 incubation were detected and structurally characterized,some of which have not been previously reported.The results demonstrated the utility of software-aided data processing tool in detection and identification of cyclic peptide metabolites.
文摘A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our 揗eshed-Bag Gathered-Bunch?method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl2,6-dioxocyclo-hexylidene)ethyl chemical protection strategy.
基金Universidad de Buenos Aires[UBACYT 2018-100246,PDE-48-2020],CONICET[PIP 11220200101898]and ANPCyT[PICT 2018-0930,PICT E 2018-0031]for partial financial support.
文摘The Antarctic fungus Cadophora malorum produces previously undescribed cyclic heptapeptides(cadophorin A and B)containing an anthranilic acid residue.The planar structure of these peptides was determined by high-resolution mass spectrometry combined with extensive 1D and 2D NMR spectroscopy.The absolute configuration of the amino acids was determined by Marfey’s method,with HPLC analysis of FDVA(Nα-(2,4-dinitro-5-fluorphenyl)-l-valinamide)derivatives making use of a PFP column.Remarkably,cadophorin 2 possesses both the uncommon d-Ile and d-allo-Ile in its structure.The peptides have metal binding properties as shown by LCMS with post column addition of metal salt solutions.These results were supported by DFT calculations.
基金supported by Doctoral Grant from Education Ministry of China(20100071110047)
文摘A highly hydrophobic cyclic peptide GG-110824,cyclo(Gly-Leu-Val-Leu-LeuVal-Pro-Ile-Gly-Leu)(C49H86N10O10),has been synthesized by a strategy combined with solid-phase synthesis(SPPS) of linear peptide and cyclization in solution.The structure including the absolute configuration of synthesized GG-110824 was confirmed by CuK radiation X-ray crystallography in the monoclinic system,space group P21 with a = 11.4966(10),b = 18.5286(2),c = 13.3943(10),= 95.03o,V = 2842.20(4)3,F(000) = 1080 and Z = 2.
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.
