Chin J, Lee S S, Lee K J, Park S, Kim D H
Department of Chemistry, McGill University, Montreal, Canada.
Nature. 1999 Sep 16;401(6750):254-7. doi: 10.1038/45751.
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 stereospecificity 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.
分子识别是众多可控分离和化学转化过程中的关键步骤，酶在执行这项任务时具有无与伦比的选择性。酶仅包含20种简单的氨基酸，但要阐明甚至预测这些立体特异性识别事件仍然很困难。尽管如此，能够立体特异性识别氨基酸的受体的合理设计正引起人们极大的兴趣，因为越来越需要以对映体纯的形式开发源自手性氨基酸中间体的治疗药物。早期的工作推动了基于小分子的高效受体的开发，但要实现氨基酸的高且可预测的立体特异性结合仍然很困难。另一方面，定向分子进化确实能筛选出与氨基酸具有高特异性结合的RNA序列或抗体，但通常无法深入了解其中涉及的分子识别机制。在此，我们展示了一种由三价钴离子和四齿配体合理设计而成的金属配合物，它能以高且可预测的区域和立体特异性结合天然氨基酸，包括简单但具有挑战性的丙氨酸。我们期望我们的方法能够实现其目标氨基酸的结合、分离以及立体特异性催化形成。
