Department of Neurofarba, University of Florence, 50019 Sesto Fiorentino, Italy.
Institut des Biomolécules Max Mousseron (IBMM), École nationale supérieure de chimie de Montpellier (ENSCM), Université de Montpellier, CEDEX 05, 34296 Montpellier, France.
Int J Mol Sci. 2019 Oct 28;20(21):5352. doi: 10.3390/ijms20215352.
Biomolecular recognition using a multivalent strategy has been successfully applied, this last decade on several biological targets, especially carbohydrate-processing enzymes, proteases, and phosphorylases. This strategy is based on the fact that multivalent interactions of several inhibitory binding units grafted on a presentation platform may enhance the binding affinity and selectivity. The zinc metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) are considered as drug targets for several pathologies, and different inhibitors found clinical applications as diuretics, antiglaucoma agents, anticonvulsants, and anticancer agents/diagnostic tools. Their main drawback is related to the lack of isoform selectivity leading to serious side effects for all pathologies in which they are employed. Thus, the multivalent approach may open new opportunities in the drug design of innovative isoform-selective carbonic anhydrase inhibitors with biomedical applications.
利用多价策略进行生物分子识别在过去十年中已成功应用于多个生物靶点，特别是碳水化合物加工酶、蛋白酶和磷酸化酶。该策略基于以下事实：多个抑制结合单元的多价相互作用接枝在呈现平台上可能会增强结合亲和力和选择性。锌金属酶碳酸酐酶（CA，EC 4.2.1.1）被认为是多种病理的药物靶点，并且发现了不同的抑制剂作为利尿剂、抗青光眼药物、抗惊厥药和抗癌药/诊断工具应用于临床。它们的主要缺点与缺乏同工酶选择性有关，导致在使用它们的所有病理中都出现严重的副作用。因此，多价方法可能为具有生物医学应用的创新同工酶选择性碳酸酐酶抑制剂的药物设计开辟新的机会。
