Identification of CJC-1131-albumin bioconjugate as a stable and bioactive GLP-1(7-36) analog

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4395-8. doi: 10.1016/j.bmcl.2004.06.066.

Abstract

A series of analogs of GLP-1(7-36) amide containing a Nepsilon-(2-[2-[2-(3-maleimidopropylamido)ethoxy]ethoxy]acetyl)lysine has been synthesized and the resulting derivatives were bioconjugated to Cys34 of human serum albumin (HSA). The GLP-1-HSA bioconjugates were analyzed in vitro to assess the stabilizing effect of bioconjugation in the presence of DPP-IV as well as GLP-1 receptor binding and activation. Compound 9 (CJC-1131) having the point of attachment to albumin at the C-terminal of GLP-1 and a D-alanine substitution at position 8 was identified as having the best combination of stability and bioactivity.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • CHO Cells
  • Cricetinae
  • Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Humans
  • Maleimides / chemistry*
  • Maleimides / metabolism*
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Protein Binding / physiology
  • Serum Albumin / metabolism*

Substances

  • CJC 1131
  • Maleimides
  • Peptide Fragments
  • Peptides
  • Serum Albumin
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon