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

Bioorg Med Chem Lett. 2015 Jan 15;25(2):302-6. doi: 10.1016/j.bmcl.2014.11.044.

Ryota Nabika ¹, Takashi L Suyama ², Andrew M Hau ², Ryosuke Misu ¹, Hiroaki Ohno ¹, Jane E Ishmael ², Kerry L McPhail ², Shinya Oishi ³, Nobutaka Fujii ⁴

Affiliations

1 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
2 Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
3 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: soishi@pharm.kyoto-u.ac.jp.
4 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: nfujii@pharm.kyoto-u.ac.jp.

PMID: 25488840 DOI: 10.1016/j.bmcl.2014.11.044

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.

Keywords

Antiproliferative peptide; Coibamide A; Depsipeptide; N-Methylamino acid.

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