Synthetic and antimicrobial studies on natural cyclopolypeptide from Caribbean marine-sponge and its analogs

ABSTRACT

Objective: A natural cyclic peptide, rolloamide, previously isolated from marine-sponge, was synthesized by coupling of tri and tetrapeptide units Boc­Phe-Pro- Val­OMe and Boc­Pro-Leu-Pro-Ile­OMe after proper deprotection at carboxyl and amino terminals followed by cyclization of linear heptapeptide segment. Design and Methodology: Solution phase technique was adopted for the synthesis of cycloheptapeptide. Required tri and tetrapeptide units were prepared by coupling of Boc-protected dipeptides viz. Boc­Phe-Pro­OH and Boc­Pro-Leu­OH with respective amino acid methyl ester hydrochloride Val-OMe.HCl and dipeptide methyl ester Pro-Ile-OMe. Cyclization of linear heptapeptide unit was done by p-nitrophenyl ester method. Similarly, two analogs of rolloamide were prepared by modification of tripeptide unit. The structures of synthesized cyclopeptide and its analogs were elucidated by spectral and elemental analysis. The newly synthesized peptide was subjected to antimicrobial screening and compared with biopotential of analogs. Results: Synthesis of cyclopeptide was accomplished with >84% yield utilizing diisopropylcarbodiimide (DIPC) as coupling agent. Newly synthesized peptide possessed promising activity against C. albicans and P. aeruginosa, K. pneumonia as compared to standard drugs, in addition to moderate activity against dermatophytes. Synthesized peptide analogs showed better antimicrobial potential against C. albicans and dermatophytes. Conclusions: Solution phase technique employing N,Ndiisopropylcarbodiimide (DIPC) and triethylamine (TEA) proved to be effective for the synthesis of natural cycloheptapeptide. N-methyl morpholine (NMM) was found to be a better base for cyclization of linear heptapeptide unit in comparison to TEA and pyridine. Promising antimicrobial potential was seen for newly synthesized cyclic peptide and its analogs.