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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Liu S,Gu W,Lo D,Ding XZ,Ujiki M,Adrian TE,Soff GA,Silverman RBdoi
10.1021/jm048952tkeywords:
subject
Has Abstractpub_date
2005-05-19 00:00:00pages
3630-8issue
10eissn
0022-2623issn
1520-4804journal_volume
48pub_type
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