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

A series of analogs of GLP-1(7–36) amide containing a Nε-(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. ▪ A series of analogs of GLP-1(7–36) amide containing a Nε-(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.