Synthesis, Characterization and Biological Evaluation of a Glycine-Rich Peptide - Cherimolacyclopeptide E

Abstract

The synthesis of a natural cyclic peptide cherimolacyclopeptide E (12) by coupling of tripeptide units Boc-gly-leu-gly-OCH 3 (9) and Boc-phe-tyr-pro-OCH 3 (10) after proper deprotection at carboxyl and amino terminals followed by cyclization of linear hexapeptide segment, is described. Structure elucidation of the cyclopeptide 12 is based on detailed spectral analysis such as FTIR, 1 H NMR, 13 C NMR, FAB MS and elemental analysis. After biological screening, the newly synthesized peptide exhibited high cytotoxicity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines with CTC 50 values of 2.76 and 4.96 μM, and potent antimicrobial activity against pathogenic microbes P. aeruginosa, E.coli and C. albicans with MICs between 12.5-6 μg/mL. Furthermore, compound 12 possessed moderate anthelmintic activity against earthworms M. konkanensis, P. corethruses and Eudrilus sp. at 2 mg/mL dose level.

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

“…The literature is enriched with reports explaining the synthesis of euryjanicin A [108], delavayin C [109], cherimolacyclopeptide G [110], psammosilenin A [111], hymenamide E [112], stylisin 1 [113], stylisin 2 [114], hymenistatin and yunnanin F [115], pseudostellarin B [116], segetalin E [117], rolloamide B [118] and pseudostellarin G [119] using the solution-phase method utilizing different carbodiimides as coupling agents, TEA/NMM as the base and the synthesis of euryjanicin B [120], mollamide [121], met-cherimolacyclopeptide B [122], axinellin A [123], phakellistatin 7 [124], phakellistatin 12 [125], petriellin A [126], hymenamide C [127], gombamide A [128] and scleritodermin A [129] by the solid-phase method of peptide synthesis. Solid-phase peptide synthesis (SPPS) results in high yields of pure products and works more quickly than classical synthesis, i.e., liquid-phase peptide synthesis (LPPS).…”

“…Structures of diverse proline-rich cyclopeptides from marine tunicates and cyanobacteria are tabulated in Figure 2. Besides this, proline-containing cyclooligopeptides are also obtained from roots, stems, barks, seeds, fruit peels of higher plants, as well as from bacteria and fungi [53,54,55,56,57,58,59,60,61,62,63,64,65,66]. …”

Total Synthesis of a Natural Cyclooligopeptide From Fruits of Sugar-Apples

“…A natural cyclic pentapeptide, fanlizhicyclopeptide B was isolated from the fruits of Annona squamosa (sugar-apples) and its structure was elucidated by ESI MS/MS, 1D and 2D NMR data and chemical degradation (Wu et al 2014). Keeping in view broad range of pharmacological activities possessed by natural cyclopeptides (Fang et al 2016;Dahiya, 2013;Dahiya and Pathak, 2006a;Pathak and Dahiya, ISSN: 2249-6041 (Print); ISSN: 2249-9245 (Online) 2 2003) and in continuation of synthetic studies of our research group toward natural peptides and their analogs (Dahiya 2007a;2007b;2007c;2008a;2008b;2008c;2008d;Dahiya and Gautam, 2010a;2010b;2010c;2011a;2011b;2011c;2011d;Dahiya and Kaur, 2007a;2008a;Dahiya and Kumar, 2007;Dahiya and Pathak, 2006b;2007a;2007b;Dahiya and Sharma, 2008;Dahiya and Singh, 2017a;2017b;2017c;Dahiya et al 2006;2009a;2009b;2009c;Kumar et al 2017), the present investigation directed toward the synthesis, structure elucidation and the biological evaluation of a sugar-apple derived cyclopentapeptide, fanlizhicyclopeptide B for the antibacterial, antifungal and anthelmintic potential.…”

First Total Synthesis and Biological Screening of a Proline-Rich Cyclopeptide from a Caribbean Marine Sponge

“…Keeping in view the broad range of pharmacological activities possessed by natural cyclopolypeptides [24,25], including the biological potential of other stylissamides (e.g., inhibitory activity towards protein translation/synthesis by Stylissamide A [26], and inhibitory activity against migration of HeLa cells by Stylissamide X [27]), the present investigation was directed toward the synthesis and structure elucidation of stylissamide G by using a solution-phase technique to obtain a natural cyclooligopeptide in the quantitative yield in the laboratory. This study was in continuation of the efforts of our research group for the total synthesis of natural bioactive cyclic peptides of marine and plant origin [28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]. Keeping in mind characteristic pattern of ‘Pro’ and ‘Phe’ units in its structure, the marine sponge tissue-derived cyclopolypeptide was further subjected to antibacterial, antifungal and anthelmintic screening.…”