Design of peptides interfering with iron-dependent regulator (IdeR) and evaluation of Mycobacterium tuberculosis growth inhibition

• Published in: Iranian journal of basic medical sciences 2017-06, Vol.20 (6), p.722-728
• Main Authors: Salimizand, Himen, Jamehdar, Saeid Amel, Nik, Leila Babaei, Sadeghian, Hamid
• Format: Article
• Language: English
• Subjects: IdeR; Inhibitor; Modeling; Mycobacterium tuberculosis; Original; Peptides; RT-PCR; Tuberculosis
• ISSN: 2008-3866; 2008-3874
• DOI: 10.22038/ijbms.2017.8859

Tuberculosis (TB), a disease caused by ( ), stayed a global health thread with high mortality rate. Since TB has a long-term treatment, it leads high risk of drug resistant development, and there is an urgent to find new drugs. The aim of this study was designing new inhibitors for a new drug target, iron dependent regulator, IdeR. Based on the interaction most populated amino acids of IdeR to the related gene operators, 50 short peptides were modeled. Bonding affinity of short peptides toward DNA were studied by docking. Top 10 best predicted bonding affinity were selected. DNA binding assay, microplate alamar blue assay, colony counting, quantitative real time- PCR (qRT-PCR) of IdeR corresponding genes, cell wall-associated mycobactin and whole-cell iron estimation were done to prove the predicted mechanism of potent constructs. Amongst the 10 synthesized short peptide candidates, glycine-valine-proline-glycine (GVPG) and arginine-proline-arginine (RPR) inhibited at 200 μM concentration. qRT-PCR showed 58-fold over expression that resulted in growth inhibition. Cell wall-associated mycobactin and whole-cell iron estimation confirmed the results of qRT-PCR. We introduced two new lead compounds to inhibit that are promising for the development of more potent anti-tubercular therapies.