New Minor Cyclic Peptides from Brachystemma calycinum

From the ethanol extract of the roots of Brachystemma calycinum D. Don, a Chinese folk herb, four new minor cyclic peptides namely brachystemin A, B, C and D (1 - 4) have been isolated. Their structures were established as cyclo (Pro(1)-Phe-Leu-Ala(1)-Thr-Pro(2)-Ala(2)-Gly) (1), cyclo (Pro(1)-Ala-Phe-Trp-Asp-Pro(2)-Leu-Gly) (2), cyclo (Pro(1)-Ile-Gly-Pro(2)-Val-Ala(1)-Ala(2)-Tyr) (3) and cyclo ( Pro-OMet-Trp-Ile-Gly-Ala-Leu-Asp) (4) respectively by means of extensive spectral methods.

Two Cyclic Peptides Produced by the Endophytic Fungus # 2221 from Castaniopsis fissa on the South China Sea Coast

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.

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.

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.

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.

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.

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.

Synthesis of Nitrogen-containing Cyclopeptides from N-Terminal Lysine Precursor on Solid Supports

Three synthetic routes for the preparation of nitrogen containing cyclic compounds have been developed, in which the assembling of Fomc-Lys(Boc) residue at N-terminal of resin-bound intermediates is a key prerequisite. Six peptides with nitrogen containing local cyclic structure were efficiently synthesized in good yield starting from chloromethyl resin.

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.

Rh(Ⅲ)-catalyzed late-stage C-H alkenylation and macrolactamization for the synthesis of cyclic peptides with unique Trp(C7)-alkene crosslinks

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.

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides

The synthesis of an Asp lactam derivative of A-183,a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity,is described.Our synthesis depends on the use of a removable backbone modification(RBM)strategy to prevent aspartimide formation,which thwarted all attempts to synthesize this target using direct solid-phase peptide synthesis.Validation of the RBM strategy in the synthesis of a second Asp lactam derivative was also accomplished.The RBM strategy is therefore proposed as a general method for the synthesis of Asp lactam cyclic peptides.

Self-Assembly of Constrained Cyclic Peptides Controlled by Ring Size

The de novo design of new peptide assemblies that expands the repertoire of biomaterial nanostructures has been of a tremendous challenge.Hence,it is evident that a successful research achievement in this area would increase the understanding of molecular interactions in supramolecules and create novel scaffolds exploitable in biotechnology and synthetic biology.The manipulation of cyclic peptide self-assembly is particularly intriguing for this purpose.Herein,we report that a novel type of cyclic peptides,referred to as chiral tether constrained cyclic peptides(CCP),shows promising self-assembly properties.CCPs are the first example of a controllable assembly of all-L-α-cyclic peptides with different ring sizes.A noteworthy feature of the CCP system is good tolerance of different secondary structures,ring size,and peptide sequence.Based on this system,a variety of nanostructures could be constructed,which display different physical properties,rendering it an excellent platform for molecular interaction studies.Further,demonstrate potential applications of these peptide assemblies in bioimaging and energy storage.

Cyclic peptides-assisted transport of metal ions across liquid-organic membrane

The formation of alkali and alkaline-earth metal picrate complexes with cyclo(Pro-Gly)n ionophores (1, n = 3; 2, n = 4) can facilitate the migration of metal ions across a bulk liquid CH2Cl2 membrane. The migration behavior was studied by measuring the solution absorption at 356 nm, using a UV/Vis spectrophotometer, and the rates can be determined by comparing the initial absorption of donor solutions with the absorption of the corresponding receiver solutions as the function of time. It was found that cyclic peptide 1 shows higher transport activity for the studied alkali and alkaline-earth metal ions than compound 2, which is related to the backbone flexibility of the cyclic peptides. The findings in this work suggest that the rate of ionophore-facilitated ion transport depends not only on the ability of complex formation in aqueous phase, but also on the ability of complex dissociation in organic phase.

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.

Cysteine-Specific Bioconjugation and Stapling of Unprotected Peptides by Chlorooximes

Cyclic peptides have found applications in fields ranging from drug discovery to nanomaterials.Peptide stapling reagents crosslink two or more residues in peptides to generate macrocycles of diverse topology and introduce linker units that might directly impact the properties and biological functions of cyclic peptides.Herein,we demonstrate that chlorooxime derivatives are cysteine-specific peptide bioconjugation and stapling reagents that generate stable thiohydroximate linkages.

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...

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.

Functional Peptides from One-bead One-compound High-throughput Screening Technique

Combinatorial chemistry provides a cost-effective method for the rapid discovery of new functional peptides.One-bead one-compound(OBOC)high-throughput screening technique offers a lot of structurally diverse peptides to be rapidly synthesized and screened for binding to a target of interest.The OBOC peptide library screening involves three main steps:library construction,positive beads separation,and peptide sequencing.This review mainly summarizes some special technique tips during functional peptide screening and potential future directions of the OBOC high-throughput screening technique.

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.