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J Med Chem. 2005 May 19;48(10):3630-8.

N-methylsansalvamide a peptide analogues. Potent new antitumor agents.

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1
Department of Chemistry, and the Drug Discovery Program, Northwestern University, Evanston, Illinois 60208-3113, USA.

Abstract

Sansalvamide A, a cyclic depsipeptide isolated from a marine fungus of the genus Fusarium, is composed of four hydrophobic amino acids (Phe, two Leu, Val) and one hydroxy acid ((S)-2-hydroxy-4-methylpentanoic acid; O-Leu) with five stereogenic centers all having S-stereochemistry. We have recently synthesized the corresponding cyclic peptide (Gu, W.; Liu, S.; Silverman, R. B. Organic Lett. 2002, 4, 4171-4174) and found that it too has antitumor activity. N-Methylation can enhance potency and selectivity for peptides. Consequently, here we synthesize 12 different N-methylated sansalvamide A peptide analogues and show that for several different tumor cell lines three of these analogues are more potent than the natural product; in pancreatic cells, sansalvamide A shows little activity, but the N-methylsansalvamide peptides are potent cytotoxic agents.

PMID:
15887970
DOI:
10.1021/jm048952t
[Indexed for MEDLINE]
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