Comparative Binding Analysis of Dipeptidyl Peptidase IV (DPP-4) with Antidiabetic Drugs - An Ab Initio Fragment Molecular Orbital Study.

ABSTRACT: Dipeptidyl peptidase IV (DPP-4) enzyme is responsible for the degradation of incretins that stimulates insulin secretion and hence inhibition of DPP-4 becomes an established approach for the treatment of type 2 diabetics. We studied the interaction between DPP-4 and its inhibitor drugs (sitagliptin 1, linagliptin 2, alogliptin 3, and teneligliptin 4) quantitatively by using fragment molecular orbital calculations at the RI-MP2/cc-pVDZ level to analyze the inhibitory activities of the drugs. Apart from having common interactions with key residues, inhibitors encompassing the DPP-4 active site extensively interact widely with the hydrophobic pocket by their hydrophobic inhibitor moieties. The cumulative hydrophobic interaction becomes stronger for these inhibitors and hence linagliptin and t

SUBMITTER: Arulmozhiraja S 

PROVIDER: S-EPMC5104442 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature