To the Editor: We wish to draw readers’ attention to the need for caution in interpreting assays of peptidases using fluorogenic substrates such as Gly-Pro-Met-2 naphthylamide (NNap). The release of the fluorophore, 2naphthylamine, may indicate the action of a tripeptidyl peptidase releasing the tripeptide, Gly-Pro-Met, but it may also result from the sequential attack of other exopeptidases, f...

UNLABELLED Dipeptidyl peptidase-4 inhibitors prevent the degradation of incretin hormones and reduce postprandial hyperglycemia in patients with type 2 diabetes mellitus. Dipeptidyl peptidase-4 degrades other peptides with a penultimate proline or alanine, including bradykinin and substance P, which are also substrates of angiotensin-converting enzyme (ACE). During ACE inhibition, substance P i...

Purpose: To investigate Pichia pastoris expression system for producing clinically usable, high-quality dipeptidyl peptidase 4 recombinant protein. Methods: The yeast, Pichia pastoris, expression system was used for the production of the human recombinant dipeptidyl peptidase 4 as a secreted form. The full-length human dipeptidyl peptidase 4 corresponding to the amino acid 31-766 was subcloned ...

A novel molecular scaffold has been synthesized, and its synthesis and incorporation into new analogues of biologically active molecules will be discussed. A comparison of the inhibitory activity of these compounds to the known type-2 diabetes compound (sitagliptin) against dipeptidyl peptidase-4 (DPP-4) will be shown.

This study represents the first large-scale study on the chemical space of inhibitors of dipeptidyl peptidase-4 (DPP4), which is a potential therapeutic protein target for the treatment of diabetes mellitus. Herein, a large set of 2,937 compounds evaluated for their ability to inhibit DPP4 was compiled from the literature. Molecular descriptors were generated from the geometrically optimized lo...

Management of type 2 diabetes mellitus (T2DM) can be challenging. Patients frequently present with poor glycemic control despite therapy. Other patients may be nonadherent or resistant to continuing their treatment when confronted with undesirable adverse effects, such as weight gain, that are associated with many conventional therapies. Incretin-based therapies developed to treat patients with...

INTRODUCTION Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the management of patients with type 2 diabetes mellitus (T2DM) and renal impairment (RI). A systematic literature review was performed to compare the efficacy and safety of DPP-4 inhibitors in patients with T2DM and RI. METHODS We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off...

The major metabolic pathway of vildagliptin in mice, rats, dogs, and humans is hydrolysis at the cyano group to produce a carboxylic acid metabolite M20.7 (LAY151), whereas the major metabolic enzyme of vildagliptin has not been identified. In the present study, we determined the contribution rate of dipeptidyl peptidase-4 (DPP-4) to the hydrolysis of vildagliptin in the liver. We performed hyd...

BACKGROUND Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU). We evaluated the efficacy and safety of this triple therapy and the characteristics of rapid responders and hypoglycemia-prone patients. METHODS We included 807 patients with type 2 diabetes who we...