Unveiling cyclic tetra amino acids-based peptides as insulin degrading enzyme inhibitors: insight from Insilico approach

Abstract

Type II diabetes has become one of the ailment that poses a grave universal wellbeing trial and the desire to curtail its dangerous activities has drawn the attention of various researchers globally. Several resistances developed by type II diabetes to series of previous drug-like small molecules has trigger the desire of researchers to attempt the use of tetra-amino acid based peptides to combat this menace. Thus, inhibiting activity of tetra amino acid based-peptides against insulin degrading enzyme (pdb id: 4re9) resulted into series of binding affinities values and (3R,6S,9S)-9-((R)-1-(benzyloxy)ethyl)-3-(((4-chlorophenyl)thio)methyl)-6-methyl-1,4,7,10-tetraazacyclododecane-2,5,8,11-tetraone (compound F) with -8.16984558kcal/mol proved to have greatest strength to inhibit the studied target. The calculated binding energy generated from molecular dynamic simulation (MDS) supported the efficiency of compound F than referenced compound (Metformin). The report from ADMET investigations were presented and interpreted accordingly.