The bulky side chain of antillatoxin is important for potent toxicity: rational design of photoresponsive cytotoxins based on SAR studies

Abstract

Antillatoxin is a cyclic peptide with potent neurotoxic and neuritogenic activities. We designed and synthesized six analogues that have photocleavable protecting groups at the terminus of the side chain. Among these compounds, the bis-o-nitrobenzyl acetal derivative was found to exhibit high toxicity and was effectively deactivated by photochemical removal, proving that the biological activity of antillatoxin was modulated by altering the size of the terminal group.