Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, 66100 Italy.
Department of Biology, Science Faculty, Selcuk University, Konya, 42130 Turkey.
Future Med Chem. 2019 Jan;11(1):5-19. doi: 10.4155/fmc-2018-0216. Epub 2018 Dec 11.
The inhibition of pancreatic lipase (PL) represents one of the most promising strategies in the search for novel antiobesity drugs. We propose here a pioneering course by exploring tripeptide scaffolds in the way to selective PL inhibitors.
METHODOLOGY/RESULTS: The peptide series exhibited good PL inhibitory properties in vitro, with all the strongest inhibitors sharing a central arginine, shown in silico to be relevant for the active site-directed activity. The compounds were found devoid of inhibitory properties on acetylcholinesterase.
Present results disclosed that basic tripeptides are able to interact efficiently with the PL-binding pocket, where they adopt a binding pose suitable for functional-to-inhibition interactions with key amino acids. Main inhibitor MALA4 may be selected as lead for further optimization.
抑制胰脂肪酶（PL）是寻找新型减肥药的最有前途的策略之一。我们在这里提出了一个开创性的研究，探索三肽支架作为选择性 PL 抑制剂。
方法/结果：该肽系列在体外表现出良好的 PL 抑制活性，所有最强的抑制剂都含有一个中央精氨酸，这在计算机模拟中显示与活性位点定向活性相关。这些化合物被发现对乙酰胆碱酯酶没有抑制作用。
本研究结果表明，碱性三肽能够有效地与 PL 结合口袋相互作用，在该口袋中，它们采用一种适合与关键氨基酸进行功能抑制相互作用的结合构象。主要抑制剂 MALA4 可被选为进一步优化的先导化合物。
