Solid-phase combinatorial synthesis of a lysyl-tRNA synthetase (LysRS) inhibitory library.


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.

DOI: 10.1021/cc700157j

Cite this paper

@article{FarreraSinfreu2008SolidphaseCS, title={Solid-phase combinatorial synthesis of a lysyl-tRNA synthetase (LysRS) inhibitory library.}, author={Josep Farrera-Sinfreu and Yaiza Espa{\~n}ol and Renaud Geslain and Tanit Guitart and Fernando Albericio and Ll{\'u}is Ribas de Pouplana and Miriam Royo}, journal={Journal of combinatorial chemistry}, year={2008}, volume={10 3}, pages={391-400} }