Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1

J Med Chem. 2008 Nov 27;51(22):7303-7. doi: 10.1021/jm8008579.


The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1. Overall, fluorinated GLP-1 analogues displayed higher proteolytic stability with simultaneous retention of biological activity (efficacy). Fluorinated amino acids are useful for engineering peptide drug candidates and probing ligand-receptor interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Chlorocebus aethiops
  • Drug Design
  • Glucagon-Like Peptide 1 / chemical synthesis
  • Glucagon-Like Peptide 1 / chemistry*
  • Halogenation
  • Leucine / analogs & derivatives*
  • Leucine / chemistry
  • Molecular Sequence Data
  • Protein Processing, Post-Translational*
  • Protein Stability


  • hexafluoroleucine
  • Glucagon-Like Peptide 1
  • Leucine