Sonker M, Yadav A
Department of Chemistry, University Institute of Engineering and Technology, CSJM University Kanpur, India.
Cent Nerv Syst Agents Med Chem. 2012 Mar;12(1):28-37. doi: 10.2174/187152412800229116.
This study highlights conformationally controlled mechanistic aspects of peptide inhibitors for BACE 1. Peptide inhibitors with reduced molecular weight tend to have cyclic conformation leading to reduced interactions with catalytic motif. Conformation plays a major role in determining potency of peptide inhibitors. An attempt has been made at designing lead compound with reduced molecular weight along with proper conformation suitable for active site and retention of specificity analogous to natural substrate. Reduced molecular weight should hopefully lead to enhanced bioavailability.
本研究突出了β-分泌酶1（BACE 1）肽抑制剂的构象控制机制方面。分子量降低的肽抑制剂往往具有环状构象，导致与催化基序的相互作用减少。构象在决定肽抑制剂的效力方面起着主要作用。已尝试设计分子量降低的先导化合物，同时具有适合活性位点的适当构象，并保留类似于天然底物的特异性。分子量降低有望提高生物利用度。
