Structural and Energetic Effects in the Molecular Recognition of Amino Acids by 18-Crown-6
Structural and Energetic Effects in the Molecular Recognition of Amino Acids by 18-Crown-6
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DOI：
10.1021/ja211021h
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发表时间：
2012-04-04
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5种氨基酸（AAs）的绝对18冠-6 （18C6）亲和力。本研究检测的氨基酸包括甘氨酸（Gly）、丙氨酸（Ala）、赖氨酸（Lys）、组氨酸（His）和精氨酸（Arg）。通过理论电子结构计算，确定了中性和质子化18C6、AAs以及由这些物质组成的质子结合配合物（AA）H+(18C6)的稳定几何形状和能量学。Gly和Ala的质子亲和比18C6低，而Lys、His和Arg的质子亲和比18C6高。因此，（AA）H+(18C6)配合物的碰撞诱导解离（CID）行为在这些体系中有显著差异。Gly和Ala配合物的CID产生H+(18C6)作为主要和最低能量的途径。在较高的能量下，由于H+(AA)形成过程中相对有利的熵变，H+(AA)与H+(18C6)竞争产生。与之相反，质子化碱性AAs的络合物的CID结果是形成H+(AA)作为唯一的直接CID产物。由于与H+(18C6)形成相关的不利的焓和熵变化，即使在较高的能量下也未观察到H+(18C6)。除了（His）H+(18C6)外，所有配合物的测量值和计算值（AA）H+-18C6键离解能（BDEs）与M06理论非常吻合，而（His）H+(18C6)的理论高估了结合强度。相比之下，B3LYP理论在所有情况下都明显低估了（AA）H+-18C6 bde。在碱性氨基酸中，Lys对18C6的结合亲和力最高，这表明Lys残基的侧链是18C6在肽和蛋白质中络合的首选结合位点。Gly和Ala比Lys表现出更强的18C6结合亲和力，这表明n端氨基为18C6提供了另一个有利的结合位点。本文研究的五种AA的18C6结合亲和趋势与AA的极化率和质子亲和率呈负相关。因此，对于Gly来说，n端氨基竞争18C6络合的能力是最好的，并且随着侧链取代基大小的增加而变得越来越不利。
Absolute 18-crown-6 (18C6) affinities of five amino acids (AAs) are determined using guided ion beam tandem mass spectrometry techniques. The AAs examined in this work include glycine (Gly), alanine (Ala), lysine (Lys), histidine (His), and arginine (Arg). Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the AAs as well as the proton bound complexes comprised of these species, (AA)H+(18C6). The proton affinities (PAs) of Gly and Ala are lower than the PA of 18C6, whereas the PAs of Lys, His, and Arg exceed that of 18C6. Therefore, the collision-induced dissociation (CID) behavior of the (AA)H+(18C6) complexes differs markedly across these systems. CID of the complexes to Gly and Ala produces H+(18C6) as the dominant and lowest energy pathway. At elevated energies, H+(AA) was produced in competition with H+(18C6) as a result of the relatively favorable entropy change in the formation of H+(AA). In contrast, CID of the complexes to the protonated basic AAs results in the formation of H+(AA) as the only direct CID product. H+(18C6) was not observed, even at elevated energies, as a result of unfavorable enthalpy and entropy change associated with its formation. Excellent agreement between the measured and calculated (AA)H+-18C6 bond dissociation energies (BDEs) is found with M06 theory for all complexes except (His)H+(18C6), where theory overestimates the strength of binding. In contrast, B3LYP theory significantly underestimates the (AA)H+-18C6 BDEs in all cases. Among the basic AAs, Lys exhibits the highest binding affinity for 18C6, suggesting that the side chains of Lys residues are the preferred binding site for 18C6 complexation in peptides and proteins. Gly and Ala exhibit greater 18C6 binding affinities than Lys, suggesting that the N-terminal amino group provides another favorable binding site for 18C6. Trends in the 18C6 binding affinities among the five AAs examined here exhibit an inverse correlation with the polarizability and proton affinity of the AA. Therefore, the ability of the N-terminal amino group to compete for 18C6 complexation is best for Gly and should become increasing less favorable as the size of the side chain substituent increases.