Chandra Koushik, Das Priyadip, Metanis Norman, Friedler Assaf, Reches Meital
Institute of Chemistry and the Centre for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem, 91904, Israel.
Department of Chemistry, Midnapore College (Autonomous), Raja Bazar Main Road, Midnapore (West), 721101, West Bengal, India.
J Pept Sci. 2017 Feb;23(2):117-121. doi: 10.1002/psc.2959. Epub 2017 Jan 10.
We have recently reported the covalent inhibition of HIV-1 integrase by an N-terminal succinimide-modified lens epithelium-derived growth factor (361-370) peptide. We also showed that this peptide is proteolytically stable. Here, we show that this inhibitor is stored as fibrils that serve as a stock for the inhibitory monomers. The fibrils increase the local concentration of the peptide at the target protein. When the monomers bind integrase, the equilibrium between the fibrils and their monomers shifts towards the formation of peptide monomers. The combination of fibril formation and subsequent proteolytic stability of the peptide may bring to new strategy for developing therapeutic agents. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
我们最近报道了一种N端琥珀酰亚胺修饰的晶状体上皮衍生生长因子（361-370）肽对HIV-1整合酶的共价抑制作用。我们还表明，这种肽在蛋白水解方面是稳定的。在此，我们表明这种抑制剂以原纤维形式储存，作为抑制性单体的储备。原纤维增加了肽在靶蛋白处的局部浓度。当单体与整合酶结合时，原纤维与其单体之间的平衡向肽单体的形成方向移动。肽的原纤维形成及其随后的蛋白水解稳定性相结合，可能为开发治疗剂带来新策略。版权所有© 2017欧洲肽学会和约翰·威利父子有限公司。
