Salimizand, Himen, Amel Jamehdar, Saeid, Babaei Nik, Leila, Sadeghian, Hamid. (1396). Design of peptides interfering with iron-dependent regulator (IdeR) and evaluation of Mycobacterium tuberculosis growth inhibition. , 20(6), 722-728. doi: 10.22038/ijbms.2017.8859
Himen Salimizand; Saeid Amel Jamehdar; Leila Babaei Nik; Hamid Sadeghian. "Design of peptides interfering with iron-dependent regulator (IdeR) and evaluation of Mycobacterium tuberculosis growth inhibition". , 20, 6, 1396, 722-728. doi: 10.22038/ijbms.2017.8859
Salimizand, Himen, Amel Jamehdar, Saeid, Babaei Nik, Leila, Sadeghian, Hamid. (1396). 'Design of peptides interfering with iron-dependent regulator (IdeR) and evaluation of Mycobacterium tuberculosis growth inhibition', , 20(6), pp. 722-728. doi: 10.22038/ijbms.2017.8859
Salimizand, Himen, Amel Jamehdar, Saeid, Babaei Nik, Leila, Sadeghian, Hamid. Design of peptides interfering with iron-dependent regulator (IdeR) and evaluation of Mycobacterium tuberculosis growth inhibition. , 1396; 20(6): 722-728. doi: 10.22038/ijbms.2017.8859

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

Iranian Journal of Basic Medical Sciences
مقاله 15، دوره 20، شماره 6، 2017، صفحه 722-728    اصل مقاله (613.46 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2017.8859
نویسندگان
Himen Salimizand1؛ Saeid Amel Jamehdar1، 2؛ Leila Babaei Nik3؛ Hamid Sadeghian* 2، 4
1Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2Antimicrobial Resistance Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
3Tuberculosis Reference Center, Dr Shariati Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
4Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad
چکیده
Objective(s): Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), 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.
Materials and Methods: 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 in silico potent constructs.
Results: Amongst the 10 synthesized short peptide candidates, glycine-valine-proline-glycine (GVPG) and arginine-proline-arginine (RPR) inhibited Mtb in vitro at 200 µM concentration. qRT-PCR showed mbtB 58-fold over expression that resulted in Mtb growth inhibition. Cell wall-associated mycobactin and whole-cell iron estimation confirmed the results of qRT-PCR.
Conclusion: We introduced two new lead compounds to inhibit Mtb that are promising for the development of more potent anti-tubercular therapies.
کلیدواژه‌ها
IdeR؛ Inhibitor؛ Modeling؛ Mycobacterium tuberculosis؛ RT-PCR
مراجع
آمار
تعداد مشاهده مقاله: 1,574
تعداد دریافت فایل اصل مقاله: 1,306
دانشگاه علوم پزشکی مشهد
آمار
تعداد نشریات29
تعداد شماره‌ها2,318
تعداد مقالات24,803
تعداد مشاهده مقاله82,159,261
تعداد دریافت فایل اصل مقاله45,368,030