Guangzhou Institutes of Biomedicine and Health, Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Chinese Academy of Sciences, No. 190, Kaiyuan Avenue, Science Park, Guangzhou, 510530, China.
Expert Opin Ther Pat. 2011 Jul;21(7):1007-22. doi: 10.1517/13543776.2011.581227. Epub 2011 Jun 9.
Bacterial enoyl acyl carrier protein reductase (ENR) specificity reduces the double bond in enoyl thioester substrates in the final enzymatic step of the elongation cycle of the fatty acid synthase-II pathway. Its function is essential for bacterial organism survival, making it an attractive target for the development of novel antibiotics. The structural features and therapeutic potential of this enzyme have stimulated the rational design of ENR inhibitors, and important progress has been achieved to date.
This review describes recent advances made in the search for ENR inhibitors, as reflected by patent applications filed from 2006 to 2010, together with an overview of the relevant literature. The first section of this paper provides a background of the biology of ENR, followed by a description of its structure and function. The main section describes the substrate specificities for ENR, and the structure-based rational design of patent inhibitors originating from different companies and academic groups.
The increase in the number of ENR inhibitors bodes well for the development of new therapeutics against multidrug-resistant bacteria. The challenge is now to improve the pharmacokinetic parameters of these inhibitors and translate them into clinical studies.
细菌烯酰酰基辅酶 A 还原酶（ENR）的特异性在脂肪酸合酶 II 途径的延伸循环的最后酶促步骤中减少烯酰硫酯底物中的双键。其功能对于细菌的生存至关重要，使其成为开发新型抗生素的有吸引力的目标。该酶的结构特征和治疗潜力激发了对 ENR 抑制剂的合理设计，迄今为止已经取得了重要进展。
本综述描述了 2006 年至 2010 年期间提交的专利申请中反映的寻找 ENR 抑制剂的最新进展，以及相关文献的概述。本文的第一部分提供了 ENR 生物学的背景，接着描述了其结构和功能。主要部分描述了 ENR 的底物特异性，以及源自不同公司和学术团体的基于结构的专利抑制剂的合理设计。
ENR 抑制剂数量的增加预示着针对多药耐药菌的新型治疗方法的发展前景良好。现在的挑战是改善这些抑制剂的药代动力学参数，并将其转化为临床研究。
