More Swati S, Vince Robert
Center for Drug Design, Academic Health Center, and Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 8-123A Weaver Densford Hall, 308 Harvard Street SE, Minneapolis, Minnesota 55455, USA.
J Med Chem. 2009 Aug 13;52(15):4650-6. doi: 10.1021/jm900382u.
A series of rational modifications to the structure of known S-(N-aryl-N-hydroxycarbamoyl)glutathione-based glyoxalase I inhibitors culminated in the discovery of the first single-digit nanomolar inhibitor. This study makes available key information about possible means to address the issues of metabolic instability, low potency, and synthetic complexicity that have plagued the area of glyoxalase I inhibition. Knowledge garnered from this study has implications in the design of inhibitors with higher conformational definition and lower peptidic character.
对已知的基于S-(N-芳基-N-羟基氨基甲酰基)谷胱甘肽的乙二醛酶I抑制剂的结构进行了一系列合理修饰，最终发现了首个个位数纳摩尔级抑制剂。这项研究提供了关键信息，有助于解决困扰乙二醛酶I抑制领域的代谢不稳定性、低活性和合成复杂性等问题。从这项研究中获得的知识对设计具有更高构象清晰度和更低肽性的抑制剂具有重要意义。
