a Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, and Laboratorio di Chimica Bioinorganica, Polo Scientifico , Università degli Studi di Firenze , Florence , Italy.
b Istituto di Bioscienze e Biorisorse , CNR , Napoli , Italy.
Expert Opin Ther Pat. 2018 Oct;28(10):745-754. doi: 10.1080/13543776.2018.1497161. Epub 2018 Jul 16.
The hydration/dehydration of CO catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1) is a crucial physiological reaction for the survival of all living organisms because it is connected with numerous biosynthetic and biochemical pathways requiring CO or HCO, such as respiration, photosynthesis, carboxylation reactions, pH homeostasis, secretion of electrolytes, transport of CO, bicarbonate, etc.
The bacterial genome encodes CAs belonging to the α-, β-, and γ-CA classes able to ensure the survival and/or satisfying the metabolic needs of the bacteria, as demonstrated by in vivo and in vitro experiments. The discovery of new anti-infectives that target new bacterial pathways, such as those involving CAs, may lead to effective therapies against diseases subject to the antibiotic resistance. This aspect is important in pharmaceutical and biomedical research but received little attention till recently.
An overview of the potential use of CAs in biomedical applications, as drug targets, bioindicators, and within artificial organs is presented. The discovery of thermostable bacterial CAs allowed the use of CAs in biotechnological applications, but patents related to the use of bacterial CAs in the development of pharmacological agents are scarce.
碳酸酐酶(CA,EC 4.2.1.1)催化的 CO 水合/脱水是所有生物生存的关键生理反应,因为它与许多需要 CO 或 HCO 的生物合成和生化途径有关,如呼吸、光合作用、羧化反应、pH 平衡、电解质分泌、CO、碳酸氢盐等的运输。
细菌基因组编码属于α、β和γ-CA 类的 CA,能够通过体内和体外实验证明其有助于细菌的生存和/或满足其代谢需求。发现针对新细菌途径的新抗感染药物,如涉及 CA 的途径,可能会导致针对抗生素耐药性疾病的有效治疗方法。这在制药和生物医学研究中很重要,但直到最近才受到关注。
本文综述了 CA 在生物医学应用中的潜在用途,包括作为药物靶点、生物标志物和人工器官。耐热细菌 CA 的发现使得 CA 能够在生物技术应用中使用,但与细菌 CA 在开发药理学制剂中的用途相关的专利却很少。