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Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A.

ABSTRACT: Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the resin and its subsequent macrolactonization. The peptide sequence of the linear coibamide A precursor was constructed on a solid-support following the optimization of the coupling conditions, where numerous coupling agents were evaluated. The macrocyclization of the resulting linear peptide provided the [d-MeAla(11)]-epimer of coibamide A, which exhibited nanomolar cytotoxic activity towards a number of human cancer cell lines.

SUBMITTER: Nabika R

PROVIDER: S-EPMC4342349 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A.

Nabika Ryota R Suyama Takashi L TL Hau Andrew M AM Misu Ryosuke R Ohno Hiroaki H Ishmael Jane E JE McPhail Kerry L KL Oishi Shinya S Fujii Nobutaka N

Bioorganic & medicinal chemistry letters 20141122 2

Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the resin and its subsequent macrolactonization. The peptide sequence of the linear coibamide A precursor was constructed on a solid-support following the optimization of the coupling ...[more]

PMID: 25488840

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