Farrera-Sinfreu Josep, Español Yaiza, Geslain Renaud, Guitart Tanit, Albericio Fernando, Ribas de Pouplana Lluís, Royo Miriam
Institute for Research in Biomedicine and Combinatorial Chemistry Unit, Barcelona Science Park, University of Barcelona, Josep Samitier 1, 08028-Barcelona, Spain.
J Comb Chem. 2008 May-Jun;10(3):391-400. doi: 10.1021/cc700157j. Epub 2008 Apr 22.
The solid-phase combinatorial synthesis of a new library with potential inhibitory activity against the cytoplasmic lysyl-tRNA synthetase (LysRS) isoform of Trypanosoma brucei is described. The library has been specifically designed to mimic the lysyl adenylate complex. The design was carried out by dividing the complex into four modular parts. Proline derivatives (cis-gamma-amino-L-proline or trans-gamma-hydroxy-L-proline) were chosen as central scaffolds. After primary screening, three compounds of the library caused in vitro inhibition of the tRNA aminoacylation reaction in the low micromolar range.
本文描述了一种新型文库的固相组合合成，该文库对布氏锥虫胞质赖氨酰 - tRNA合成酶（LysRS）亚型具有潜在抑制活性。该文库经过专门设计以模拟赖氨酰腺苷酸复合物。设计过程是将该复合物分为四个模块部分。选择脯氨酸衍生物（顺式 - γ - 氨基 - L - 脯氨酸或反式 - γ - 羟基 - L - 脯氨酸）作为核心支架。经过初步筛选，文库中的三种化合物在低微摩尔范围内对tRNA氨酰化反应产生了体外抑制作用。
