A new strategy applied to the synthesis of an α-helical bicyclic peptide constrained by two overlapping i, i+7 side-chain bridges of novel design

Chongxi Yu, John W. Taylor

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

A conformationally constrained, bicyclic, 14-residue peptide containing two overlapping i, i+7 side-chain bridges has been synthesized. The design of the side-chain linkage, which is built around a p-substituted benzene ring for rigidity, and the solid-phase approach applied to the peptide synthesis, are both new. A Boc/Benzyl peptide chain assembly method was combined with Fmoc/OFm orthogonal side-chain deprotection and solid-phase cyclization to form the first side-chain lactam bridge. A 2-(2-pyridyl)ethyl group (2-Pet), activated by methylation with CH3I in DMF, was then used in combination with Fmoc to allow a second orthogonal side-chain deprotection and solid-phase cyclization to form the second bridge. The circular dichroism spectrum of the product indicates that it is highly helical.

Original languageEnglish (US)
Pages (from-to)1731-1734
Number of pages4
JournalTetrahedron Letters
Volume37
Issue number11
DOIs
StatePublished - Mar 11 1996

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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