Solid-phase synthesis of tris-benzamides as α-helix mimetics

Tae Kyung Lee, Jung Mo Ahn

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Small molecules mimicking α-helices are of great interest since numerous protein-protein interactions use helical structures at the interface. With a goal of generating libraries of α-helix mimetics, an efficient solid-phase synthetic method was developed to produce tris-benzamides. The tris-benzamide scaffold was designed to place three side-chain functional groups found at the i, i + 4, and i + 7 positions of an α-helix, emulating one helical face. The synthetic strategy involves simple and iterative reactions of removal of an allyl ester, formation of an amide bond via an O → N acyl migration, and an O-alkylation. A small library of twenty tris-benzamides containing a variety of functional groups was prepared in high purity (83-99%) to demonstrate the versatility of the synthetic approach. This methodology allowed the facile and rapid construction of α-helix mimetics that would facilitate the identification of small molecules for target proteins.

Original languageEnglish (US)
Pages (from-to)107-111
Number of pages5
JournalACS Combinatorial Science
Volume13
Issue number2
DOIs
StatePublished - Mar 14 2011

Keywords

  • Protein-protein interaction
  • Solid-phase synthesis
  • Tris-benzamide scaffold
  • α-helix mimetics

ASJC Scopus subject areas

  • Chemistry(all)

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