GLP-1-[7-37]-NH2 N端区域与受体相互作用及cAMP产生的结构要求
Structural requirements of the N-terminal region of GLP-1-[7-37]-NH2 for receptor interaction and cAMP production.
作者信息
Sarrauste de Menthière Cyril, Chavanieu Alain, Grassy Gérard, Dalle Stéphane, Salazar Guillermo, Kervran Alain, Pfeiffer Bruno, Renard Pierre, Delagrange Philippe, Manechez Dominique, Bakes David, Ktorza Alain, Calas Bernard
机构信息
Centre de Biochimie Structurale, CNRS UMR 5048 - UM1 - INSERM UMR 554, 29 rue de Navacelles, 34090 Montpellier Cedex, France.
出版信息
Eur J Med Chem. 2004 Jun;39(6):473-80. doi: 10.1016/j.ejmech.2004.02.002.
A series of GLP-1-[7-36]-NH(2) (tGLP-1) and GLP-1-[7-37] analogs modified in position 7, 8, 9 and 36, have been designed and evaluated on murine GLP-1 receptors expressed in RIN T3 cells for both their affinity and activity. Ten of the synthesized peptides were found full agonists with activities superior or at least equal to that of the native hormone. Five of them were investigated for their plasmatic stability and the most stable, [a(8)-desR(36)]GLP-1-[7-37]- NH(2) (Compound 8), evaluated in vivo in a glucose tolerance test which confirmed a clearly longer activity than that of the native hormone. We also performed circular dichroism study and propose a hypothetical structural model explaining the most part of observed activities of GLP-1 analogs on RIN T3 cells.
设计了一系列在第7、8、9和36位进行修饰的GLP-1-[7-36]-NH₂（tGLP-1）和GLP-1-[7-37]类似物，并在RIN T3细胞中表达的小鼠GLP-1受体上对其亲和力和活性进行了评估。发现所合成的十种肽为完全激动剂，其活性优于或至少等同于天然激素。对其中五种进行了血浆稳定性研究，最稳定的[a(8)-desR(36)]GLP-1-[7-37]-NH₂（化合物8）在葡萄糖耐量试验中进行了体内评估，证实其活性明显长于天然激素。我们还进行了圆二色性研究，并提出了一个假设的结构模型，该模型解释了GLP-1类似物在RIN T3细胞上观察到的大部分活性。
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