| Abstract
| - Apicidins are a class of cyclic tetrapeptides that do not contain the classical electrophilic α-ketoepoxide yet are potent (nM) inhibitors of histone deacetylase and antiprotozoal agents. Thesecompounds showed broad-spectrum activities against the apicomplexan family of protozoa includingPlasmodium sp (malarial parasite), Toxoplasma gondii, Cryptosporidium sp., and Eimeria sp. Thesecyclic peptides contain a β-turn amino acid (R)-Pip or (R)-Pro, (S)-N-methoxy Trp, (S)-Ile, or (S)-Val, and either (S)-2-amino-8-oxodecanoic acid or a modified (S)-2-amino-8-oxodecanoic acid. Theisolation and structure elucidation of new apicidins from two Fusarium species, temperature-dependent NMR studies of apicidin, NMR and molecular modeling based conformation of the 12-membered macrocyclic ring, and selected chemical modifications of apicidin have been detailed inthis paper. The cyclic nature of the peptide, the C-8 keto group, and the tryptophan are all criticalfor the biological activity.
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