A new tri-orthogonal strategy for peptide cyclization

Org Lett. 2002 Sep 19;4(19):3219-21. doi: 10.1021/ol026416u.

Abstract

A solid phase tri-orthogonal protection/cleavage strategy that uses acidic, basic, and neutral conditions is described. Strategically protected alpha-azido-gamma-9-fluorenylmethyl-L-glutamate (1) and alpha-azido-epsilon-N-Fmoc-L-lysine (2) were incorporated into growing peptides on Wang resin using a novel azide protection strategy. These residues, separated by 1-3 monomers, were deprotected at the side chains and cyclized via lactam formation. The N-terminus was further functionalized to extend the chain. This method represents a straightforward protocol for peptide cyclization on solid support.

MeSH terms

  • Amino Acids
  • Binding Sites
  • Catalysis
  • Cross-Linking Reagents
  • Cyclization
  • Peptides / chemistry*
  • Peptides, Cyclic / chemical synthesis*
  • Protein Conformation

Substances

  • Amino Acids
  • Cross-Linking Reagents
  • Peptides
  • Peptides, Cyclic