Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
Biochimie. 2010 Nov;92(11):1509-29. doi: 10.1016/j.biochi.2010.04.026. Epub 2010 May 10.
Aminopeptidases are enzymes that selectively hydrolyze an amino acid residue from the N-terminus of proteins and peptides. They are important for the proper functioning of prokaryotic and eukaryotic cells, but very often are central players in the devastating human diseases like cancer, malaria and diabetes. The largest aminopeptidase group include enzymes containing metal ion(s) in their active centers, which often determines the type of inhibitors that are the most suitable for them. Effective ligands mostly bind in a non-covalent mode by forming complexes with the metal ion(s). Here, we present several approaches for the design of inhibitors for metallo-aminopeptidases. The optimized structures should be considered as potential leads in the drug discovery process against endogenous and infectious diseases.
氨肽酶是一类能够从蛋白质和肽的 N 端选择性地水解掉一个氨基酸残基的酶。它们对原核细胞和真核细胞的正常功能至关重要，但在癌症、疟疾和糖尿病等严重人类疾病中往往是关键因素。最大的氨肽酶组包括在其活性中心含有金属离子的酶，这通常决定了最适合它们的抑制剂类型。有效的配体主要通过与金属离子形成配合物以非共价的方式结合。在这里，我们提出了几种设计金属氨肽酶抑制剂的方法。优化后的结构可以被认为是针对内源性和传染性疾病的药物发现过程中的潜在先导化合物。
