Hemendra Gautam

Cyclopolypeptides are among the most predominant biomolecules in nature, especially those derived from plant seeds. This category of compounds has gained extraordinary attention due to remarkable variety of structures and valuable biofunctions. These congeners display enormous variation in terms of both structure and function and are the most significant biomolecules due to their widespread bioproperties. The estrogenic activity, immunosuppressive activity, cytotoxicity, vasorelaxant activity, and other properties possessed by cyclic peptides from seeds of plants make these congeners attractive leads for the drug discovery process. The current study covers the important structural features, structure–activity relationship, synthesis methods, and bioproperties of plant seeds‐originated bioactive peptides from Vaccaria segetalis, Linum usitatissimum, and Goniothalamus leiocarpus, which may prove vital for the development of novel therapeutics based on a peptide skeleton.

Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a wide spectrum of exceptional and potent bioproperties. Because of their complex nature and size divergence, thiazole-based peptides (TBPs) bestow a pivotal chemical platform in drug discovery processes to generate competent scaffolds for regulating allosteric binding sites and peptide–peptide interactions. The present study dissertates on the natural reservoirs and exclusive structural components of marine-originated TBPs, with a special focus on their most pertinent pharmacological profiles, which may impart vital resources for the development of novel peptide-based therapeutic agents.

In present study, it was of interest to synthesize a natural proline-rich cyclooligopeptide - cyclomontanin D 8 by coupling of tripeptide Boc-L-Asn(bzh)-L-Pro-Gly-OH and tetrapeptide L-Leu-L-Pro-L-Tyr-L-Ala-OMe followed by cyclization of linear polypeptide fragment. Structure of synthesized cyclopeptide was confirmed by detailed spectral analysis including FTIR, 1H NMR, 13C NMR, ESIMS/MS and elemental analysis. From the results of biological evaluation, it was concluded that newly synthesized cyclooligopeptide possessed good bioactivity against Gram-negative bacteriaKlebsiella pneumonia, Pseudomonas aeruginosa as well as potent antidermatophyte activity against Microsporum audouinii and Trichophyton mentagrophytes, in comparison to reference drugs - ciprofloxacin and griseofulvin. Moreover, 8 exhibited moderate antifungal activity against pathogenic Candida albicans with minimum inhibitory concentration (MIC) value of 6 mg/ml. Key words: Annona montana, cyclomontanin D, cyclic heptapeptide, peptide synthesis, antibacterial activity, antidermatophyte activity.

The first synthesis of a naturally occurring tetrapeptide cyclo-(isoleucyl-prolyl-leucyl-alanyl) has been achieved using a solution-phase technique via coupling of dipeptide segments Boc-l-Pro-l-Leu-OH and l-Ala-l-Ile-OMe. Deprotection of the linear tetrapeptide unit and its subsequent cyclization gave a cyclopeptide, identical in all aspects to the naturally occurring compound. Bioactivity results indicated the antifungal and antihelmintic potential of the synthesized peptide against pathogenic dermatophytes and earthworms.

The present study deals with the synthesis of a novel proline-rich cyclopeptide - gypsin B 7 via coupling of tripeptide units Boc-l-Tyr-l-Phe-l-Pro-OH and Gly-l-Leu-l-Pro-OMe utilizing two different carbodiimides, followed by cyclization of linear polypeptide fragment. Structure elucidation of newly synthesized peptide was done on basis of FT-IR, 1H-NMR, 13C-NMR, ESI-MS/MS data. From biological evaluation, it was concluded that cyclic hexapeptide 7 exhibited potent antidermatophyte activity against pathogenic Microsporum audouinii andTrichophyton mentagrophytes. Also, good bioactivity against pathogenicCandida albicans and gram-negative bacteria, and moderate antihelmintic activity against three species of earthworms was observed for newly synthesized cyclohexapeptide. Key words: Gypsophila arabica, cyclic hexapeptide, gypsin B, peptide coupling, antimicrobial activity, antihelmintic activity.

The present study deals with the first total synthesis of the proline-rich cyclopolypeptide stylisin 2 via a solution phase technique by coupling of the Boc-l-Pro-l-Ile-l-Pro-OH tripeptide unit with the l-Phe-l-Pro-l-Pro-l-Tyr-OMe tetrapeptide unit, followed by cyclization of the resulting linear heptapeptide fragment. The chemical structure of the finally synthesized peptide was elucidated by FTIR, ¹H/¹³C-NMR and FAB MS spectral data, as well as elemental analyses. The newly synthesized peptide was subjected to antimicrobial screening against eight pathogenic microbes and found to exhibit potent antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, in addition to moderate antidermatophyte activity against pathogenic Trichophyton mentagrophytes and Microsporum audouinii when compared to standard drugs—gatifloxacin and griseofulvin.