Synthetic and biological studies on a cyclopolypeptide of plant origin

A natural cyclic peptide previously isolated from Citrus medica was synthesized by coupling of tetrapeptide 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.

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 different pharmacological activities including antimicrobial, anthelmintic and cytotoxic activities.

Synthesis of sarcodactylamide 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.

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.