Total synthesis and cyclization strategy of samoamide A, a cytotoxic cyclic octapeptide rich in proline and phenlalanine isolated from marine cyanobacterium

Abstract

Samoamide A is a cyclic octapeptide rich in proline and phenylalanine residues isolated from an American Samoa marine cyanobacterium, which exhibits potent activity against H460 human non-small-cell lung cancer cells (IC₅₀ of 1.1 μM). The first total synthesis of samoamide A was achieved by employing a strategy of a solid-phase peptide synthesis (SPPS) and a head-to-tail cyclization selecting free steric–hinrance connection sites. Then the final product was purified and identified. This strategy not only provides a basis in producing potent cytotoxic agents for drug discovery, but also provides a reference to the total synthesis of proline-rich peptides.

Keywords:

• Cyclic peptide
• samoamide A
• solid-phase synthesis
• cyclization

Acknowledgment

We are grateful to the Instrumental Analysis Center of Ocean University of China for NMR spectroscopic and mass spectrometric analysis.