Adenosine 5′-triphosphate (ATp4-):: Aspects of the coordination chemistry of a multitalented biological substrate
Adenosine 5′-triphosphate (ATp4-):: Aspects of the coordination chemistry of a multitalented biological substrate
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DOI：
10.1351/pac200476020375
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发表时间：
2004-02-01
影响因子：
1.8
通讯作者：
Sigel, H
中科院分区：
文献类型：
--
作者：
Sigel, H
首先，介绍了ATP（4-）的自堆积特性以及金属离子和质子对这些特性的影响。讨论了磷酸盐配位的金属离子（M2+）和M（ATP）（2-）中腺嘌呤残基的N7之间形成大螯合物的一些例子，然后考虑由ATP（4-），M2+和氨基酸阴离子组成的混合配体络合物，其侧链允许与腺嘌呤部分的芳环堆积或疏水相互作用;这产生了选择性。接下来，研究二磷酸化9-[2-（膦酰甲氧基）乙基]腺嘌呤（PMEA（2-）;阿德福韦）的性质，即，比较了PMEApp（4-）与（2 '-脱氧）ATP（4-）的金属离子结合性质，从而解释了PMEApp（2-）最初是核酸聚合酶的优良底物的原因。当然，在PMEA残基掺入生长的核酸链后，其被终止，这就是PMEA发挥其抗病毒特性的方式[其双（新戊酰氧基甲基）酯，阿德福韦酯，最近被批准用于B肝炎治疗]。最后，自由能的变化与（宏观）螯合物的形成或分子内堆积相互作用和减少的介电常数的溶剂上的络合物的稳定性和它们在溶液中的结构的影响被认为是。
Firstly, the self-stacking properties of ATP(4-) and the effects of metal ions and protons on these properties are described. Some examples involving macrochelate formation between phosphate-coordinated metal ions (M2+) and N7 of the adenine residue in M(ATP)(2-) are discussed, and this is followed by considerations on mixed ligand complexes consisting of ATP(4-), M2+, and amino acid anions with side chains that allow either aromatic-ring stacking or hydrophobic interactions with the adenine moiety; this gives rise to selectivity. Next, the properties of diphosphorylated 9-[2-(phosphonomethoxy)ethyl] adenine (PMEA(2-); Adefovir), i.e., of PMEApp(4-), are compared with those of (2'-deoxy)ATP(4-) with regard to their metal ion-binding qualities, and in this way it can be explained why PMEApp(2-) is initially an excellent substrate for nucleic acid polymerases. Of course, after incorporation of the PMEA residue into the growing nucleic acid chain, this is terminated and this is how PMEA exerts its antiviral properties [its bis(pivaloyloxymethyl)ester, Adefovir dipivoxil, was recently approved for use in hepatitis B therapy]. Finally, the change in free energy connected with (macro)chelate formation or intramolecular stacking interactions and the effect of a reduced dielectric constant of the solvent on the stability of complexes and their structures in solution is considered.