Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology

Hiroshi Sato, Masahito Yoshida, Hayato Murase, Hiroshi Nakagawa, Takayuki Doi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Combinatorial synthesis and biological evaluation of cyclodepsipeptide destruxin B have been achieved. The cyclization precursors were prepared by solid-phase peptide synthesis via a split and pool method utilizing SynPhase lanterns with colored tags and cogs, followed by cleavage from the polymer-support. Macrolactonization utilizing MNBA-DMAPO in solution-phase was successfully performed in parallel to afford the desired 64-member destruxin analogues in moderate to good yields. Biological evaluation of the synthesized analogues indicated that a MeAla residue for the building block A is required to induce the desired morphological changes in osteoclast-like multinuclear cells (OCLs), and introduction of the substituent at the R4 position of a proline moiety is tolerated by the morphology and may enable the preparation of a molecular probe for the target identification in the osteoclasts.

Original languageEnglish
Pages (from-to)590-595
Number of pages6
JournalACS Combinatorial Science
Volume18
Issue number9
DOIs
Publication statusPublished - 2016 Sep 12

Keywords

  • combinatorial library
  • cyclic peptides
  • cyclodepsipeptides
  • osteoclasts
  • solid-phase synthesis

ASJC Scopus subject areas

  • Chemistry(all)

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