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Structural analysis of bengamide derivatives as inhibitors of methionine aminopeptidases.

ABSTRACT: Natural-product-derived bengamides possess potent antiproliferative activity and target human methionine aminopeptidases (MetAPs) for their cellular effects. Several derivatives were designed, synthesized, and evaluated as MetAP inhibitors. Here, we present four new X-ray structures of human MetAP1 in complex with the inhibitors. Together with the previous structures of bengamide derivatives with human MetAP2 and tubercular MtMetAP1c, analysis of the interactions of these inhibitors at the active site provides structural basis for further modification of these bengamide inhibitors for improved potency and selectivity as anticancer and antibacterial therapeutics.

SUBMITTER: Xu W

PROVIDER: S-EPMC3470909 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Structural analysis of bengamide derivatives as inhibitors of methionine aminopeptidases.

Xu Wei W Lu Jing-Ping JP Ye Qi-Zhuang QZ

Journal of medicinal chemistry 20120914 18

Natural-product-derived bengamides possess potent antiproliferative activity and target human methionine aminopeptidases (MetAPs) for their cellular effects. Several derivatives were designed, synthesized, and evaluated as MetAP inhibitors. Here, we present four new X-ray structures of human MetAP1 in complex with the inhibitors. Together with the previous structures of bengamide derivatives with human MetAP2 and tubercular MtMetAP1c, analysis of the interactions of these inhibitors at the activ ...[more]

PMID: 22913487

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