鉴定CJC-1131-白蛋白生物共轭物为一种稳定且具有生物活性的胰高血糖素样肽-1(7-36)类似物。
Identification of CJC-1131-albumin bioconjugate as a stable and bioactive GLP-1(7-36) analog.
作者信息
Léger Roger, Thibaudeau Karen, Robitaille Martin, Quraishi Omar, van Wyk Pieter, Bousquet-Gagnon Nathalie, Carette Julie, Castaigne Jean-Paul, Bridon Dominique P
机构信息
Research Department, ConjuChem Inc., 225 President-Kennedy Ave., Suite 3950, Montréal, QC, Canada H2XY8.
出版信息
Bioorg Med Chem Lett. 2004 Sep 6;14(17):4395-8. doi: 10.1016/j.bmcl.2004.06.066.
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.
一系列含有Nε-(2-[2-[2-(3-马来酰亚胺基丙基酰胺基)乙氧基]乙氧基]乙酰基)赖氨酸的GLP-1(7-36)酰胺类似物已被合成，所得衍生物与人血清白蛋白(HSA)的Cys34进行了生物偶联。对GLP-1-HSA生物偶联物进行了体外分析，以评估在二肽基肽酶-IV (DPP-IV)存在下生物偶联的稳定作用以及GLP-1受体结合和激活情况。化合物9 (CJC-1131)在GLP-1的C末端与白蛋白连接，且在第8位有一个D-丙氨酸取代，被确定为具有稳定性和生物活性的最佳组合。
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