Uccello-Barretta Gloria, Balzano Federica, Aiello Federica, Vanni Letizia, Mori Mattia, Menta Sergio, Calcaterra Andrea, Botta Bruno
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via G. Moruzzi 3, 56124 Pisa, Italy.
Org Biomol Chem. 2015 Jan 21;13(3):916-24. doi: 10.1039/c4ob01936a.
The stereochemical features of 2,8,14,20-tetrakis(D-leucyl-D-valinamido)resorc[4]arenecarboxylic acid and the N-succinyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanine-4-nitroanilide polypeptide substrate were investigated by nuclear magnetic resonance spectroscopy. Proton selective relaxation parameters gave the basis for the inhibitory activity of resorcin[4]arene in the hydrolysis of the polypeptide substrate by α-chymotrypsin. Results showed that an interaction between the resorcin[4]arene and α-chymotrypsin does occur, and involves the hydrophobic moiety of the macrocycle. This interaction is further reinforced by polar groups located on the side chains of the resorcin[4]arene, whereas the macrocycle-polypeptide substrate interaction is negligible. Conformational analysis and interaction studies carried out by molecular modeling are in good agreement with the NMR data, thus providing an additional support to the rationalization of the inhibitory potential of resorcin[4]arenes on the α-chymotrypsin activity.
通过核磁共振光谱研究了2,8,14,20-四（D-亮氨酰-D-缬氨酰胺基）间苯二酚[4]芳烃羧酸和N-琥珀酰-L-丙氨酰-L-丙氨酰-L-脯氨酰-L-苯丙氨酸-4-硝基苯胺多肽底物的立体化学特征。质子选择性弛豫参数为间苯二酚[4]芳烃抑制α-胰凝乳蛋白酶水解多肽底物的活性提供了依据。结果表明，间苯二酚[4]芳烃与α-胰凝乳蛋白酶之间确实发生了相互作用，且涉及大环的疏水部分。位于间苯二酚[4]芳烃侧链上的极性基团进一步加强了这种相互作用，而大环与多肽底物之间的相互作用可忽略不计。通过分子模拟进行的构象分析和相互作用研究与核磁共振数据高度吻合，从而为阐释间苯二酚[4]芳烃对α-胰凝乳蛋白酶活性的抑制潜力提供了额外支持。
