De-Novo Drug Design of Shorter Chain Peptide as Antitubercular Agents

Tuberculosis remains a deadly disease throughout worldwide and the emergence of Multidrug resistance makes us an urgent need to find a therapeutic lead using bio-friendly shorter chain peptides. 200 peptide templates (di, tri,tetra & penta peptide 50 each) were selected for rational drug design approach viz., Lipinski filters, Boman index, molinspiration & Swiss dock procedure in which 1 amino acid was mandatory chosen from past literature survey & the rest of combinations by trite and trial basis. Among the results obtained from Lipinski only 13 peptides, namely (Try-Asp, Ile-Arg, Leu-Arg, Glu-Arg, Asp-Glu, Asp-Pro-Phe, Gly-Ala-Asp, Met-Asp-Val, Gly-Ala- Leu-Asp, Pro-Gly-Asp-Ala, Gly-Ala-Leu-Arg-Ser, & Ala-Cys-Gly-Ser-Asp are predicted to be best outcome leads against tuberculosis. Further among 13 leads subjected to Boman index calculations & molecular properties of molinspiration, we found that 9 leads were considered as better targets (rejected leads : Pro-Gly-Asp-Ala, Gly-Ala- Asp, Gly-Ala-Leu-Arg-Ser, Ala-Cys-Gly-Ser-Asp for both HGPRT enzyme and TLR-2 receptor. Among the 9 leads subjected to docking against Hypoxanthine Guanine Phospho Ribosyl Transferase enzyme & Toll like receptor 2, we found that dipeptide Glu-Arg (D-E) is considered to be the most potent therapeutic lead against HGPRT enzyme with its full fitness energy as -395546 k.cal/mols and the dipeptide Asp-Glu (D-E) was found to be the most potent therapeutic lead against TLR-2 receptor for TB with its full fitness energy as -978870 k.ca/mol respectively. Further these dipeptide lead can be explored to test preclinical efficacy & comparison of therapeutic potency will be validated through structure based drug design in near future.