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A metal complex that binds α-amino acids with high and predictable stereospecificity

机译:以高且可预测的立体特异性结合α-氨基酸的金属络合物

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Molecular recognition is the key step in a wide range of controlled separation and chemical transformation processes, with enzymes performing this task with an unsurpassed degree of selectivity. Enzymes contain only 20 simple amino acids, yet it remains difficult to rationalize or even predict these stereospecific recognition events. Nonetheless, the rational design of receptors able to recognize amino acids stereospecifically is attracting considerable interest because therapeutic drugs, that may be developed from chiral amino acid intermediates, are increasingly required in enantiomerically pure form. Early work has stimulated the development of efficient receptors based on small molecules, but binding of amino acids with high and predictable stereo-specificity remains difficult to achieve. Directed molecular evolution, on the other hand, does select for RNA sequences or antibodies that bind amino acids with high specificity, but typically without providing insights into the molecular recognition mechanisms involved. Here we show that a rationally designed metal complex formed from a trivalent cobalt ion and a tetradentate ligand binds natural amino acids, including the simple yet challenging amino acid alanine, with high and predictable regio- and stereospecificity. We expect that our approach will allow the binding as well as separation and stereospecific catalytic formation of its target amino acids.
机译:分子识别是广泛受控分离和化学转化过程中的关键步骤,其中酶以无与伦比的选择性完成这项任务。酶仅包含20个简单氨基酸,但是仍然很难合理化甚至预测这些立体特异性识别事件。但是,能够立体定向识别氨基酸的受体的合理设计引起了相当大的兴趣,因为对映体纯形式日益需要可以由手性氨基酸中间体开发的治疗药物。早期的工作刺激了基于小分子的有效受体的发展,但是仍然难以实现具有高且可预测的立体特异性的氨基酸结合。另一方面,定向分子进化的确选择了具有高特异性的结合氨基酸的RNA序列或抗体,但通常没有深入了解所涉及的分子识别机制。在这里,我们显示了由三价钴离子和四齿配体形成的合理设计的金属配合物,结合了天然氨基酸,包括简单但具有挑战性的氨基酸丙氨酸,具有很高且可预测的区域和立体特异性。我们期望我们的方法将允许其目标氨基酸的结合以及分离和立体定向催化形成。

著录项

  • 来源
    《Nature》 |1999年第6750期|p.254-257|共4页
  • 作者单位
  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
  • 关键词

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