Influence of charge and structure on the coordination chemistry of copper aminoglycosides.
Influence of charge and structure on the coordination chemistry of copper aminoglycosides.
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电荷和结构对氨基糖苷铜配位化学的影响。
DOI：
10.1039/c0dt00704h
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Cowan,JA
中科院分区：
文献类型：
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作者：
Patwardhan,Anjali;Cowan,JA
氨基糖苷类是一类基于2-脱氧链霉胺环的分子，其被含有邻位胺和羟基官能团的各种糖单元官能化。这些带正电荷的胺促进与细菌16 s rRNA的选择性高亲和力结合，从而产生抗菌活性。氨基糖苷类还显示出选择性靶向多种治疗相关的RNA基序，并且与铜组合以促进RNA靶标的不可逆降解。在多个环上存在多个羟基和胺基团产生了许多潜在的铜配位位点。然而，只有一个小的子集，这些网站实际上结合铜，这还没有明确定义的实验，在这里，我们描述了一个更广泛的六个氨基糖苷类（卡那霉素A，卡那霉素B，新霉素B，新霉胺，妥布霉素和巴龙霉素）的配合物的结构表征，提供见解的因素，有助于协调选择性的氨基糖苷类对二价铜。能够螯合铜离子的邻位配体供体的存在似乎是稳定金属结合的先决条件，其中电荷密度提供KD的进一步调整。金属配位抗菌活性的可能作用也被认为是。
Aminoglycosides are a family of molecules based on a 2-deoxystreptamine ring that is functionalized with a variety of sugar units that contain vicinal amine and hydroxyl functionality. These positively-charged amines promote selective high affinity binding to bacterial 16 s rRNA with resultant antibacterial activity. Aminoglycosides have also been shown to selectively target a variety of therapeutically relevant RNA motifs, and in combination with copper to promote irreversible degradation of the RNA target. The presence of multiple hydroxyl and amine groups on multiple rings creates many potential copper coordination sites. However, only a small subset of these sites actually bind copper, which have not been clearly defined experimentally, Herein we describe a more extensive structural characterization of the complexes of six aminoglycosides (kanamycin A, kanamycin B, neomycin B, neamine, tobramycin and paromomycin) that provide insights on the factors contributing to the coordination selectivity of aminoglycosides toward divalent copper. The presence of vicinal ligand donors capable of chelating the copper ion appears to be a prerequisite for stable metal binding, with charge density providing further tuning of the KD. A possible role for metal coordination in antibacterial activity is also considered.