Xu Zhigang, DiCesare John C, Baures Paul W
Department of Chemistry and Biochemistry, The University of Tulsa, Tulsa, Oklahoma 74104, USA.
J Comb Chem. 2010 Mar 8;12(2):248-54. doi: 10.1021/cc1000105.
A library of oligomeric compounds was synthesized based on the imidazole-4,5-dicarboxylic acid scaffold along with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate nonpolar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala), and were designed to be useful in screening for inhibitors of protein-protein interactions. Many of the protected and deprotected oligomers show evidence of conformational isomers persistent at room temperature in aqueous solution. A total of 317 final oligomers, out of 441 targeted compounds, were obtained in high analytical purity and of sufficient quantity to submit them for high-throughput screening as part of the NIH Roadmap.
基于咪唑-4,5-二羧酸支架，合成了一个寡聚化合物库，该库还包含氨基酸酯以及由氨基酸衍生的手性二胺。最终化合物包含非极性氨基酸（亮氨酸、苯丙氨酸、色氨酸）、极性氨基酸（丝氨酸、天冬氨酸、精氨酸）和中性氨基酸（甘氨酸、丙氨酸），并且设计用于筛选蛋白质-蛋白质相互作用的抑制剂。许多被保护和脱保护的寡聚物显示出在室温下于水溶液中存在构象异构体的证据。在441种目标化合物中，总共获得了317种最终寡聚物，其具有高分析纯度且数量充足，可作为美国国立卫生研究院路线图的一部分提交进行高通量筛选。
