Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 14, Issue 17, Pages 4395-4398Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2004.06.066
Keywords
GLP-1; albumin conjugate; DPP-IV
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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. (C) 2004 Elsevier Ltd. All rights reserved.
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