Optimization Of Isocitrate Lyase Peptide Inhibitor Screening

Tuberculosis is a chronic communicable disease caused by Mycobacterium tuberculosis and spread around the world, about200million people died of TB each year all over the word. Previous studies showed that after taken up by macrophages, Mycobacterium tuberculosis becomes persistent in them and sustains life through the glyoxylate bypass. As isocitrate lyase (ICL) is a key rate-limiting enzyme in the the glyoxylate bypass and a decisive factor in mycobacterial persistence, it was selected as the target of new anti-tubercular drugs.Using the computer simulation technology of docking and the phage peptide library for optimize the Isocitrate lyase peptide inhibitor screening. First screened the binding peptides by phage peptide library, which has a high affinity with isocitrate lyase(ICL). And then uses of the Discovery Studio2.1simulate docking with peptides and ICL protein crystal (1F8I). Finally, using the solid-phase synthesis of Fmoc for synthesize peptide, and detecting their biological activity. We get29heptadpeptide sequences by phage peptide library screening,12of them can successfully docking with ICL protein crystal. The biological activity detecting showed that, they all have conspicuous inhibited on the ICL activity (rate of inhibition over50%).In this study, we optimized the screening of ICL inhibitor, used computer simulation of docking, and successfully screened out of the peptide inhibitor with conspicuous inhibited on the ICL activity, so as to lay a solid foundation for developing new anti-TB drugs with isocitrate lyase as a target.