Winum Jean-Yves, Scozzafava Andrea, Montero Jean-Louis, Supuran Claudiu T
Institut des Biomolécules Max Mousseron UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
Curr Pharm Des. 2008;14(7):615-21. doi: 10.2174/138161208783877848.
Zinc ion plays a crucial role in the protein's functions and is linked to a variety of physiological processes. It constitutes an essential component of numerous enzymes especially carbonic anhydrase (CAs, EC 4.2.1.1), a pharmaceutically-important metalloprotein which catalyses efficiently the reversible hydration of carbon dioxide to bicarbonate with discharge of a proton. The potential therapeutic applications of selective carbonic anhydrase inhibitors has become an important challenge over the last few years, as some isoforms of this enzyme on the 16 described in higher vertebrates have been found to be involved in important pathologies such as cancer, obesity and ophthalmologic diseases. Coordination of the inhibitor with the zinc ion present in the active site is an important determinant which has to be taken into consideration for the design of isozyme-specific and organ-selective inhibitors. Besides the well known sulfonamide function, others zinc binding groups have been described constituting a new platform for the development of novel pharmacological agents. In this review, recent studies on the discovery of new zinc binding function will be discussed.
锌离子在该蛋白质的功能中起着至关重要的作用，并与多种生理过程相关联。它是众多酶的重要组成部分，尤其是碳酸酐酶（CAs，EC 4.2.1.1），这是一种具有重要药学意义的金属蛋白，能高效催化二氧化碳可逆水合生成碳酸氢根并释放一个质子。在过去几年中，选择性碳酸酐酶抑制剂的潜在治疗应用已成为一项重要挑战，因为在高等脊椎动物中描述的该酶的16种同工型中，有些已被发现与癌症、肥胖症和眼科疾病等重要病理状况有关。抑制剂与活性位点中存在的锌离子的配位是一个重要决定因素，在设计同工酶特异性和器官选择性抑制剂时必须予以考虑。除了众所周知的磺酰胺功能外，还描述了其他锌结合基团，它们构成了开发新型药物的新平台。在这篇综述中，将讨论关于发现新的锌结合功能的最新研究。
