DNA Cleavage by a Nine-Membered Masked Enediyne, an Analogue of the Kedarcidin and C-1027 Chromophores

摘要

Kedarcidin (KD) and C-1027 belong to a new class of chromoprotein antitumor antibiotics consisting of a 1:1 complex of apoproteins and cytotoxic nonprotein chromophores. Their chromophores. KD-chr (1) and C-1027-chr (2). possess a common nine-memberedenediyne core structure. Their biological activities are associated with their ability to cause strong DNA cleavage. The proposed mechanism of the DNA cleavage is that biradical species generated from the highly strained nine-membered enediyne chromophores abstract hydrogens from de-oxyribose. Unlike other enediynes, C-1027 shows predominant DNA-cleaving activity even in the absence of thiols or reducing agents, a valuable implication for its application as a potent cancer chemotherapeutic agent.