Structural and Energetic Effects in the Molecular Recognition of Protonated Peptidomimetic Bases by 18-Crown-6
Structural and Energetic Effects in the Molecular Recognition of Protonated Peptidomimetic Bases by 18-Crown-6
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DOI：
10.1021/ja2102345
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发表时间：
2012-02-01
影响因子：
15
通讯作者：
Rodgers, M. T.
中科院分区：
文献类型：
--
作者：
Chen, Yu;Rodgers, M. T.
采用离子束串联质谱技术测定了9个质子化拟肽碱基的绝对18冠-6 （18C6）亲和。本工作中包含的碱基(B)是末端氨基氨基和碱性氨基酸侧链的模拟物，即18C6与肽和蛋白质结合的有利位点。选择异丙胺作为n端氨基的模拟物，选择咪唑和4-甲基咪唑作为组氨酸（His）侧链的模拟物，选择1-甲基胍作为精氨酸（Arg）侧链的模拟物，以及包括甲胺、乙胺、正丙胺、正丁胺和1,5-二氨基戊烷在内的几种主要胺作为赖氨酸（Lys）侧链的模拟物。进行了理论电子结构计算，以确定中性和质子化的18C6和拟肽碱的稳定几何形状和能量学，以及由这些物质组成的质子结合配合物(B)H+(18C6)。Lys侧链模拟物的18C6结合亲和力大于Arg和His模拟物的结合亲和力。这些结果表明，赖氨酸侧链应该是18C6与肽和蛋白质络合的首选结合位点。目前的研究结果还表明，Arg或His与Lys对18C6的竞争并不显著。n端氨基的模拟物对18C6的结合亲和力与Lys侧链模拟物相似或更高。然而，理论表明，与n端氨基模拟物的结合弱于与所有赖氨酸模拟物的结合。这些结果表明，n端氨基可能与Lys侧链竞争18C6络合。
Absolute 18-crown-6 (18C6) affinities of nine protonated peptidomimetic bases are determined using guided ion beam tandem mass spectrometry techniques. The bases (B) included in this work are mimics for the terminal amino amino group and the side chains of the basic amino acids, i.e., the favorable sites for binding of 18C6 to peptides and proteins. Isopropylamine is chosen as a mimic for the n-terminal amino group, imidazole and 4-methylimidazole are chosen as mimics for the side chain of histidine (His), 1-methylguanidine is chosen as a mimic for the side chain of arginine (Arg), and several primary amines including methylamine, ethylamine, n-propylamine, n-butylamine, and 1,5-diamino pentane as mimics for the side chain of lysine (Lys). Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the peptidomimetic bases, as well as the proton bound complexes comprised of these species, (B)H+(18C6). The measured 18C6 binding affinities of the Lys side chain mimics are larger than the measured binding affinities of the mimics for Arg and His. These results suggest that the Lys side chains should be the preferred binding sites for 18C6 complexation to peptides and proteins. Present results also suggest that competition between Arg or His and Lys for 18C6 is not significant. The mimic for the n-terminal amino group exhibits a measured binding affinity for 18C6 that is similar to or greater than that of the Lys side chain mimics. However, theory suggests that binding to n-terminal amino group mimic is weaker than that to all of the Lys mimics. These results suggest that the n-terminal amino group may compete with the Lys side chains for 18C6 complexation.