Two New Cyclic Peptides from Psammosilene tunicoides

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.

Synthesis of a highly hydrophobic cyclic decapeptide by solid-phase synthesis of linear peptide and cyclization in solution

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 solubilization...

Dock-able linear and homodetic di, tri, tetra and pentapeptide library from canonical amino acids: SARS-CoV-2 Mpro as a case study

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.

Investigation of the interaction between HIV-1 DNA and cyclic peptides by electrospray ionization mass spectrometry

The interaction between HIV-1 DNA and five cyclic peptides （CP1-CP5） was investigated using electrospray ionization mass spectrometry （ESI-MS）. It revealed that CP1 [c（Ala-Tyr-Leu-Ala-Gly）] and CP4 [c（Pro-D-Tyr-Leu-D-Ala-Gly）] have the higher binding affinity with the duplex DNA among the five cyclic peptides.

Structural and Electronic Properties of Cyclic Peptide-gold Nanoparticle as a Drug Delivery System

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.

Anti-metastatic Effect of Repeated Cyclic-GRGDSPA Peptide Produced by Intein Protein Trans-splicing on Murine B16 Melanoma Cells

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

Synthesis and Crystallization of a Cyclic Decapeptide GG-110824

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.

Software-aided detection and structural characterization of cyclic peptide metabolites in biological matrix by high-resolution mass spectrometry

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.

SYNTHESIS OF CYCLIC PEPTIDES USING BBC REAGENT

We report here the synthesis of cyclic peptides using benzotriazolyloxy-bis(pyrrolidino)-carbonium hexafluoro- phosphate(BBC)as a coupling reagent with high yield and speed even in low concentration compared with the other usual coupling reagents.

Cyclic heptapeptides with metal binding properties isolated from the fungus Cadophora malorum from Antarctic soil

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.

A COMPARISON OF THE DETERMINATION OF STABILITY CONSTANTS OF COMPLEXES OF Cd(Ⅱ)WITH AMINO ACIDS AND SIMPLE PEPTIDES USING MICRO—pH—METRIC TITRATIONS AND CYCLIC VOLTAMMETRY

This paper reports the determination of stability constants for complexes of Cd(Ⅱ)with Gly, Ala,Val,Asp,Gly—Asp,Asp Gly,Gly—Gly and Gly—Gly—Gly using both micro—pH—metric titra- tions and the application of convolution—deconvolution cyclic voltammetry at 25℃ and I=0.10 mol· dm^(-3)(KNO_3).Stability constants were calculated from pH—metric data using the SUPERQUAD com- puter program and cyclic voltammograms were collected,stored and manipulated using the EG and G CONDECON 300 software.A considerably larger ligand:metal ratio(e,g.50:1)was possible using voltammetry.Evaluation of results from the two techniques suggests that stability constants for the species[CdL_2]and[CdL_3]are reliable when calculated fromvoltammetry while those for[CdL]are more reliable when determined by pH-metric titration.

Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through thecGMP/cGMP-dependent protein kinase pathway

AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.

Synthetic and biological studies on a cyclopolypeptide of plant origin

Objective:A natural cyclic peptide previously isolated from Citrus medica was synthesized by coupling of tetrapep-tide units Boc-Leu-Pro-Trp-Leu-OMe and Boc-Ile-Ala-Ala-Gly-OMe after proper deprotection at carboxyl and amino terminals followed by cyclization of linear octapeptide segment. Methods:Solution phase technique was adopted for the synthesis of cyclooctapeptide-sarcodactylamide. Required tetrapeptide units were prepared by coupling of Boc-protected dipeptides viz. Boc-Leu-Pro-OH and Boc-Ile-Ala-OH with respective dipeptide methyl esters Trp-Leu-OMe and Ala-Gly-OMe. Cyclization of linear octapeptide unit was done by p-nitrophenyl ester method. The structure of synthesized cyclopolypeptide was elucidated by FTIR,1H NMR,13C NMR,FABMS spectral data and elemental analysis. The newly synthesized peptide was evaluated for dif-ferent pharmacological activities including antimicrobial,anthelmintic and cytotoxic activities. Results:Synthesis of sarcodac-tylamide was accomplished with >78% yield utilizing dicyclohexylcarbodiimide(DCC) as coupling agent. Newly synthesized peptide possessed potent cytotoxic activity against Dalton's lymphoma ascites(DLA) and Ehrlich's ascites carcinoma(EAC) cell lines,in addition to moderate anthelmintic activity against earthworms Megascoplex konkanensis,Pontoscotex corethruses and Eudrilus sp. Moreover,cyclopolypeptide displayed good antimicrobial activity against pathogenic fungi Candida albicans and Gram-negative bacteria Pseudomonas aeruginosa,in comparison to standard drugs griseofulvin and ciprofloxacin. Conclusion:Solution phase technique employing DCC and triethylamine(TEA) as base proved to be effective for the synthesis of natural cyclooctapeptide. N-methyl morpholine(NMM) was found to be a better base for the cyclization of linear octapeptide unit in comparison to TEA and pyridine.

Synthetic Channel-forming Peptides and Ion Selectivity

Introduction Peptides made up of alternating L- and D- amino acids can form β-helices as in gramicidin A or cyclic peptides that aggregate to form tubes In both cases the structures are hollow with all the side chains projecting outwards. Kennedy et al. postulated that. peptides having the （LLLD）n configuration could form helices with every fourth side chain projecting inward. It is a fact that synthetic N-formyl- （LeuSerLeuGly） 6- OH, when added to a lipid bilayer, dimerizes, to form ion channels having conductances greater than that of gramicidin.

Solvent Effect on Conformation of a Cycloheptapeptide,Stylopeptide 1,Evaluated by Molecular Dynamics in Methonal and Aqueous Environments

Stylopeptide 1 synthesized and isolated from different sources exhibits a large activity difference in inhibitory effect on the growth of a cancer cell.Based on the different amounts of methanol and water during synthesis,isolation and purification of the cyclic peptides,molecular dynamics(MD) was employed to simulate the conformation of stylopeptide 1 in methanol and aqueous environments.The comparative results show that the backbone ring was more rigid in methanol than in water.In methanol,two β-turns and three hydrogen bonds were well conserved throughout the simulation,whereas no hydrogen bonds or turns were preserved in water.The activity difference of stylopeptide 1 seemed to be attributed to the solvent effect on its conformation.

CDFI血流信号分级、抗CCP抗体、G6PI、RF对类风湿性关节炎的诊断价值

目的分析彩色多普勒血流显像(CDFI)血流信号分级、抗环瓜氨酸肽抗体(CCP)、葡萄糖6磷酸异构酶(G6PI)、类风湿因子(RF)对类风湿性关节炎(RA)的诊断价值。方法回顾性选取2022年4月至2023年10月新疆医科大学附属中医医院收治的100例RA患者纳入观察组,根据病情分为RA活动期组(n=50)和RA非活动期组(n=50);依据血流信号CDFI分级分为0~1级组(n=20)、2级组(n=17)、3级组(n=13)。选取同期本院收治的100例其他自身免疫性疾病患者纳入对照组。比较观察组、对照组一般临床资料(性别、病程、年龄、RA家族史、体重指数、吸烟史、饮酒史、居住地、职业等),比较不同活动期患者抗CCP抗体、G6PI及RF水平;比较不同血流信号分级组患者抗CCP抗体、G6PI及RF水平;采用受试者工作特征(ROC)曲线评估CDFI血流信号分级、抗CCP抗体、G6PI、RF联合检测对RA的诊断价值。结果两组患者性别构成比、病程、年龄、RA家族史、体重指数、吸烟史、饮酒史、居住地、职业比较,差异均无统计学意义(P>0.05);观察组患者抗CCP抗体、G6PI及RF水平均高于对照组,差异均有统计学意义(P<0.05)。RA活动期组患者抗CCP抗体、G6PI及RF水平均高于RA非活动期组患者,差异均有统计学意义(P<0.05)。血流信号3级组患者抗CCP抗体、G6PI及RF水平均高于血流信号0-1级组、2级组患者,差异均有统计学意义(P<0.05)。CDFI血流信号分级、抗CCP抗体、G6PI、RF单独检测RA的敏感度分别为79.57%、86.45%、82.14%、77.89%,特异度分别为83.89%、79.28%、83.67%、84.15%,AUC分别为0.855(0.804~0.907)、0.940(905~0.976)、0.893(0.852~0.935)、0.800(0.736~0.864),CDFI血流信号分级、抗CCP抗体、G6PI、RF联合检测RA的敏感度为89.36%,特异度为77.24%,AUC为0.957(0.933~0.980)。结论RA患者血清CCP抗体、G6PI、RF水平升高,随着CDFI血流信号分级增大,升高愈加明显,CDFI血流信号分级、抗CCP抗体、G6PI、RF联合检测RA诊断价值较高,对判断RA进展具有意义。

抗MCV抗体、抗CCP抗体对类风湿关节炎的诊断价值及其与疾病活动度的相关性

目的探讨抗突变型瓜氨酸波形蛋白(MCV)抗体、抗环瓜氨酸肽(CCP)抗体对类风湿关节炎(RA)的诊断价值,并分析其与RA疾病活动度的相关性。方法选取74例RA患者(RA组)、95例结缔组织病患者(非RA组)和60例健康体检者(健康对照组)作为研究对象。基于红细胞沉降率的28个关节疾病活动度评分(DAS28-ESR)将RA组患者分为高活动期组(n=22)、中活动期组(n=18)、低活动期组(n=14)和缓解期组(n=20)。比较RA组、非RA组、健康对照组之间的血清抗MCV抗体、血清抗CCP抗体、血清类风湿因子(RF)和ESR阳性率,以及RA不同活动期组之间的血清抗MCV抗体水平、血清抗CCP抗体水平、血清RF水平和ESR。通过绘制受试者工作特征曲线分析血清抗MCV抗体水平、血清抗CCP抗体水平、血清RF水平和ESR单独及联合诊断RA的价值。分析RA组患者血清抗MCV抗体水平、血清抗CCP抗体水平、血清RF水平和ESR与DAS28-ESR的相关性。结果(1)RA组的血清抗MCV抗体、血清抗CCP抗体、血清RF和ESR阳性率高于非RA组和健康对照组(P<0.05);非RA组的血清抗CCP抗体、血清RF和ESR阳性率高于健康对照组(P<0.05),但两组的血清抗MCV抗体阳性率差异无统计学意义(P>0.05)。(2)缓解期组、低活动期组、中活动期组、高活动期组的血清抗MCV抗体水平、血清抗CCP抗体水平和ESR依次升高(P<0.05);高活动期组血清RF水平高于其他3组(P<0.05),其他3组之间的血清RF水平差异无统计学意义(P>0.05)。(3)血清抗MCV抗体水平、血清抗CCP抗体水平单独诊断RA的曲线下面积(AUC)均>0.85,且均大于血清RF水平和ESR的AUC(P<0.05);血清抗MCV抗体水平与血清抗CCP抗体水平诊断RA的敏感度、特异度、AUC差异无统计学意义(P>0.05);血清抗MCV抗体水平、血清抗CCP抗体水平、血清RF水平和ESR联合诊断RA的AUC达0.935,大于任意单一指标诊断RA的AUC(P<0.05)。(4)RA患者的血清抗MCV抗体水平、血清抗CCP抗体水平和ESR与DAS28-ESR均呈正相关(P<0.05)。结论相比于传统指标血清RF和ESR,血清抗MCV抗体和血清抗CCP抗体对RA均有较高的诊断价值;将二者联合血清RF和ESR用于诊断RA,可明显提高诊断效能。血清抗MCV抗体水平、血清抗CCP抗体水平均与RA疾病活动度呈正相关,可作为评估患者疾病活动度的辅助指标。

血清信号素3A在类风湿关节炎的诊断价值

目的通过检测血清信号素3A(Sema3A)在类风湿关节炎(RA)中的表达水平,探讨其对RA的诊断价值。方法随机选取到赣州市人民医院就诊者并分为三组:(1)RA组(病情活动性RA 51例,病情非活动性RA 52例)。(2)非RA组患者93例。(3)健康对照组(HC)50例。采用酶联免疫吸附法(ELISA)检测血清中Sema3A、抗环瓜氨酸多肽抗体(anti-CCP)和抗RA33抗体(anti-RA33);散射比浊法检测类风湿因子(RF)和C-反应蛋白(CRP);魏氏法检测红细胞沉降率(ESR)。结果RA组血清Sema3A、anti-CCP、RF和anti-RA33表达水平分别为(27.15±8.19)ng/ml、131.31(399.50)U/ml、105.90(167.50)U/ml和30.80(23.80)U/ml,与非RA组和HC组比较,结果具有统计学差异。Sema3A对RA诊断的曲线下面积为0.76,标准误为0.03,95%可信区间(95%CI)为0.70~0.82。ROC曲线分析各项指标对RA的诊断显示,特异度最高的是anti-CCP(Sp=0.92),灵敏度最高的是RF(Se=0.83),约登指数和曲线下面积最高的是anti-CCP(YDI=0.73,AUC=0.85)。RA病情活动组和非活动组血清Sema3A水平比较具有统计学差异(P<0.01),血清Sema3A与ESR、CRP、DAS28均呈负相关(r=-0.54,r=-0.66,r=-0.42,P<0.01)。结论Sema3A对RA患者具有良好诊断价值,与非RA患者比较具有鉴别诊断价值,且可以用来判断RA疾病的严重程度。