Modification Of Isocitrate Lyase Peptide Inhibitor

Tuberculosis is composed of Mycobacterium tuberculosis Mycobacterium, chronic infectious disease caused by existing research shows that after med tuberculosis bacili engulfed by macrophages, in macrophages to hold state, obtain energy through glyoxylate cycle, to maintain its long-term are retained in the in the host. Isocitrate lyase (isocitrate lyase, ICL) is one of the key enzyme of speed of glyoxylate cycle approach, to maintain its n/med tuberculosis bacili withholding was crucial status, so we choose to isocitrate lyase (ICL) as the new anti-tb drug targets. Has been active in vitro experiments showed that the amino acid sequence for [NPPERSP] linear peptide of isocitrate lyase has obvious inhibitory effect.Solid-phase synthesis of Fmoc was used to synthesis cyclic peptide by the known isocitrate lyase linear peptide sequence according to the end to end way. Mass spectrometry demonstrated that the measured value of relative molecular mass was consistent with the theoretical value. Inhibition test confirmed that the Cyclic peptide showed significant inhibition to the ICL activity(The inhibition rate was more than50%). At the same time, half-life of linear peptide and cyclic peptide in plasma were measured by HPLC. Results indicated that, half-life of Cyclic peptide in plasma achieved llmin, which increased by175%comparing with linear peptide.This study after linear peptide synthesis of cyclic peptide, increase the stability of peptide drug structure, make its half-life in plasma, which can effectively increase the therapeutic effects of time after drug into the body, to develop new type of isocitrate lyase peptide inhibitors to provide theoretical basis.