Synthesis of a dicarba analogue of human β-defensin-1 using a combined ring closing metathesis--native chemical ligation strategy

Org Lett. 2012 Feb 3;14(3):878-81. doi: 10.1021/ol203407z. Epub 2012 Jan 12.


We herein describe the first synthesis of the native antimicrobial protein HBD-1 making use of an orthogonal thiol protection strategy and a novel dicarba analogue thereof. The robust hydrocarbon linkage was installed by replacement of one disulfide bond using on-resin ring closing metathesis. The unprecedented 59-membered C-terminal cysteine macrocyclic fragment thus formed then engages in native chemical ligation allowing convergent access to this unique synthetic protein analogue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Disulfides / chemistry
  • Humans
  • Molecular Sequence Data
  • Oxidation-Reduction
  • beta-Defensins / chemistry*


  • DEFB1 protein, human
  • Disulfides
  • beta-Defensins