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 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.
Léger
Roger
R
Research Department, ConjuChem Inc., 225 President-Kennedy Ave., Suite 3950, Montréal, QC, Canada H2XY8. leger@conjuchem.com
Thibaudeau
Karen
K
Robitaille
Martin
M
Quraishi
Omar
O
van Wyk
Pieter
P
Bousquet-Gagnon
Nathalie
N
Carette
Julie
J
Castaigne
Jean-Paul
JP
Bridon
Dominique P
DP
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006801:Humans; D008301:Maleimides / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012709:Serum Albumin / Q000378:metabolism*
C473712:CJC 1131; D008301:Maleimides; D010446:Peptide Fragments; D010455:Peptides; D012709:Serum Albumin; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon