Pinkin Nicholas K, Liu Ina, Abron Jessicca D, Waters Marcey L
Department of Chemistry, CB 3290, University of North Carolina, Chapel Hill, NC 27599 (USA).
Chemistry. 2015 Dec 1;21(49):17981-6. doi: 10.1002/chem.201502302. Epub 2015 Oct 21.
We have systematically studied how secondary interactions with neighboring lysine (Lys) and arginine (Arg) residues influence the binding and selectivity of the synthetic receptor A2 N for trimethyllysine (Kme3 ). Multiple secondary binding sites on A2 N are formed by carboxylates rigidly positioned over aromatic rings, a motif that has been shown to stabilize salt bridges. We varied the spacing between KmeX (X=0, 3) and an ancillary Lys or Arg and measured binding by isothermal titration calorimetry (ITC). These studies revealed that both neighboring residues improve the binding of A2 N to KmeX by approximately 1 kcal mol(-1) , with little influence of the spacing. Nonetheless, the improvement in affinity caused by Arg is enthalpically driven, while for Lys it is entropically driven, suggesting different mechanisms by which the residues interact with the secondary binding site.
我们系统地研究了与相邻赖氨酸（Lys）和精氨酸（Arg）残基的二级相互作用如何影响合成受体A2 N对三甲基赖氨酸（Kme3 ）的结合和选择性。A2 N上的多个二级结合位点由刚性定位在芳环上的羧酸盐形成，该基序已被证明可稳定盐桥。我们改变了KmeX（X = 0, 3）与辅助Lys或Arg之间的间距，并通过等温滴定量热法（ITC）测量结合情况。这些研究表明，两个相邻残基均可使A2 N与KmeX的结合提高约1 kcal mol(-1) ，间距影响较小。尽管如此，Arg引起的亲和力提高是由焓驱动的，而Lys引起的则是由熵驱动的，这表明这些残基与二级结合位点相互作用的机制不同。
