Wysocka Magdalena, Gruba Natalia, Grzywa Renata, Giełdoń Artur, Bąchor Remigiusz, Brzozowski Krzysztof, Sieńczyk Marcin, Dieter Jenne, Szewczuk Zbigniew, Rolka Krzysztof, Lesner Adam
Faculty of Chemistry, University of Gdansk, Gdansk Poland.
Faculty of Chemistry, Wroclaw Technical University, Wroclaw, Poland.
Sci Rep. 2016 Mar 9;6:22856. doi: 10.1038/srep22856.
Herein we present the synthesis of a novel type of peptidomimetics composed of repeating diaminopropionic acid residues modified with structurally diverse heterobifunctional polyethylene glycol chains (abbreviated as DAPEG). Based on the developed compounds, a library of fluorogenic substrates was synthesized. Further library deconvolution towards human neutrophil serine protease 4 (NSP4) yielded highly sensitive and selective internally quenched peptidomimetic substrates. In silico analysis of the obtained peptidomimetics revealed the presence of an interaction network with distant subsites located on the enzyme surface.
在此，我们展示了一种新型拟肽的合成，该拟肽由重复的二氨基丙酸残基组成，这些残基用结构多样的异双功能聚乙二醇链修饰（简称为DAPEG）。基于所开发的化合物，合成了一个荧光底物文库。对人中性粒细胞丝氨酸蛋白酶4（NSP4）进行进一步的文库去卷积分析，得到了高度敏感和选择性的内部淬灭拟肽底物。对所得拟肽的计算机分析揭示了与位于酶表面远处亚位点的相互作用网络的存在。
