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

Abstract

A natural heptacyclopeptide, stylissamide G (7), previously isolated from the Bahamian marine sponge Stylissa caribica from the Caribbean Sea, was synthesized via coupling of the tetrapeptide l-phenylalanyl-l-prolyl-l-phenylalanyl-l-proline methyl ester with the tripeptide Boc-l-leucyl-l-isoleucyl-l-proline, followed by cyclization of the linear heptapeptide fragment. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FT-IR, 1H NMR, 13C NMR and mass spectrometry. Results of pharmacological activity studies indicated that the newly synthesized cycloheptapeptide displayed good anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniea at 2 mg/mL and in addition, potent antifungal activity against pathogenic Candida albicans and dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL.

Keywords

• stylissamide G
• cycloheptapeptide
• Stylissa caribica
• peptide synthesis
• macrocyclization
• pharmacological activity
• marine sponge