Carullo Gabriele, Perri Mariarita, Manetti Fabrizio, Aiello Francesca, Caroleo Maria Cristina, Cione Erika
Department of Pharmacy, Health and Nutritional Sciences, "Dipartimento di Eccellenza 2018-2022", University of Calabria, Edificio Polifunzionale, 87036 Rende, Italy.
Department of Biotechnology, Chemistry and Pharmacy, "Dipartimento di Eccellenza 2018-2022", University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy.
Bioorg Med Chem Lett. 2019 Jul 15;29(14):1761-1764. doi: 10.1016/j.bmcl.2019.05.018. Epub 2019 May 13.
The G-protein-coupled receptor 40 (GPR40) is an attractive molecular target for the treatment of type 2 diabetes mellitus. Previously, based on the natural oleic acid substrate, an exogenous ligand for this receptor, named AV1, was synthesized. In this context, here we validated the activity of AV1 as a full agonist, while the corresponding catechol analogue, named AV2, was investigated for the first time. The ligand-protein interaction between this new molecule and the receptor was highlighted in the lower portion of the GPR40 groove that generally accommodates DC260126. The functional assays performed have demonstrated that AV2 is a suitable GPR40 partial agonist, showing a therapeutic potential and representing a useful tool in the management of type 2 diabetes.
G蛋白偶联受体40（GPR40）是治疗2型糖尿病颇具吸引力的分子靶点。此前，基于天然油酸底物，合成了该受体的一种外源性配体，命名为AV1。在此背景下，我们在此验证了AV1作为完全激动剂的活性，同时首次对相应的儿茶酚类似物AV2进行了研究。这种新分子与受体之间的配体-蛋白质相互作用在通常容纳DC260126的GPR40凹槽下部得以凸显。所进行的功能试验表明，AV2是一种合适的GPR40部分激动剂，具有治疗潜力，是2型糖尿病管理中的一种有用工具。
