Department of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
Bioorg Med Chem Lett. 2013 Sep 1;23(17):4832-6. doi: 10.1016/j.bmcl.2013.07.024. Epub 2013 Jul 23.
Endoplasmic reticulum aminopeptidases, ERAP1 and ERAP2, as well as Insulin regulated aminopeptidase (IRAP) play key roles in antigen processing, and have recently emerged as biologically important targets for manipulation of antigen presentation. Taking advantage of the available structural and substrate-selectivity data for these enzymes, we have rationally designed a new series of inhibitors that display low micromolar activity. The selectivity profile for these three highly homologous aminopeptidases provides a promising avenue for modulating intracellular antigen processing.
内质网氨肽酶 1（ERAP1）和内质网氨肽酶 2（ERAP2）以及胰岛素调节氨肽酶（IRAP）在抗原加工中发挥着关键作用，并且最近已成为影响抗原呈递的重要生物学靶点。利用这些酶的现有结构和底物选择性数据，我们合理设计了一系列具有低微摩尔活性的新型抑制剂。这三种高度同源的氨肽酶的选择性特征为调节细胞内抗原加工提供了一个很有前途的途径。
