Abstract
Recently recognized class of oral hypoglycemic, dipeptidyl peptidase (DPP4) inhibitors could block the dipeptidyl peptidase 4 (DPP4) enzymes. DPP4 is an intrinsic membrane glycoprotein and a serine exopeptidase that plays a major role in glucose metabolism and responsible for the degradation of incretins such as GLP-1, therefore providing a useful treatment to diabetes mellitus type 2. The present work focused on the study of the structural homology modeling of dipeptidyl peptidase 4 [Homo sapiens] (NP_001926). The Ramachandran plot of DPP4 (NP_001926.2) has 88.9% residues in the most favoured region while template 2QT9 has 96.1% residues in the most favoured region. The model was validated by using protein structure tools RAMPAGE and Prochek for reliability. Docking studies were further performed to analyze the interaction mode between selected DPP4 inhibitor anagliptin derivative SKK and receptor DPP4 by using Hex 8.0.0. The in-silico analysis was useful to identify the novel inhibitor that illustrates better activity than the other reported inhibitors.
Highlights
Diabetes mellitus is a prime public health problem and forthcoming epidemic all over the globe [38] disorder caused due to insufficient or ineffective insulin [2]
Dipeptidyl peptidase-4 (DPP4) encoded by the DPP4 gene and it is a membrane serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides [12; 40]
Several studies demonstrated that the inhibition of DPP4 could increase the amount of circulating glucagon-like peptide 1 (GLP-1) to improve the secretion of insulin in the body [43]
Summary
Diabetes mellitus is a prime public health problem and forthcoming epidemic all over the globe [38] disorder caused due to insufficient or ineffective insulin [2]. The combination therapeutics or oral monotherapy with other anti-diabetic agents used to control diabetes through clinical anti-diabetes therapy [16]. These anti-diabetic agents may cause adverse side effects and chronic complications [6; 25]. DPP-4 inhibitors recommended for use in patients with T2DM therapy, that including hypoglycaemia incidences, risks of cardiovascular complications and weight gain [14]. It is a rather indiscriminate enzyme for which a diverse range of substrates are known. It has regarded as promising target to develop novel drug for treatment of type 2 diabetes
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