2026-10-11T17:58:13Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33941183 2026-09-19T03:05:35Z category_1 category_4 category_13 category_14 category_16 category_19 category_21 category_873 category_135 portal_63 item_type_3 month_year_09_2026

Discovery of Novel Peptides as DPP-IV Inhibitors: In Silico Screening, Molecular Dynamics Simulations, and Preliminary In Vitro Evaluation Burak Calis (25074467) Fernando Berton Zanchi (14060942) Beyza Canakcimaksutoglu (25074470) Ahmet E. Yetiman (21357758) Ozkan Fidan (6496958) Biophysics Biochemistry Genetics Molecular Biology Physiology Pharmacology Biotechnology Chemical Sciences not elsewhere classified Computational Biology molecular dynamics simulations lower predicted likelihood incretin hormone glucagon including molecular docking impaired insulin secretion free energy scores downstream experimental validation better membrane permeability antimicrobial peptide databases 26 candidate peptides iv inhibitor candidates dipeptidyl peptidase iv favorable predicted dpp 1r binding preference iv inhibitors based discover novel dpp vitro </ italic silico </ italic vitro </ silico </ novel peptides binding affinity iv inhibitors peptide library peptide 3 like peptide − 16 − 15 structural similarity significant role screened using proteolytic degradation prolonged half pharmacokinetic profiling pharmacokinetic characteristics peptides 3 optimal absorption native form inhibition rate human body highly susceptible glucose homeostasis findings indicate 5 kcal Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder characterized by impaired insulin secretion, which leads to obesity. The incretin hormone glucagon-like peptide-1 (GLP-1) has a significant role in glucose homeostasis, but its native form in the human body is highly susceptible to proteolytic degradation by dipeptidyl peptidase IV (DPP-IV). In this study, a peptide library was constructed from antimicrobial peptide databases to discover novel DPP-IV inhibitors based on structural similarity to that of native GLP-1. A total of 26 candidate peptides were shortlisted and screened using <i>in silico</i> analysis, including molecular docking, pharmacokinetic profiling, and molecular dynamics simulations. Particularly, two of the candidate antimicrobial peptides showed potent binding affinity to DPP-IV, with free energy scores of −15.6 and −16.5 kcal/mol, surpassing the binding affinity of native GLP-1 for DPP-IV. These peptides also exhibited lower predicted binding affinities for the GLP-1 receptor (GLP-1R) than for DPP-IV, suggesting a potential selective inhibitory effect and, consequently, a lower predicted likelihood of interfering with native GLP-1 signaling. Pharmacokinetic characteristics of the peptides were promising with an optimal absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile, along with prolonged half-life and stability. Because of its better membrane permeability and more favorable predicted DPP-IV/GLP-1R binding preference, peptide 3 was further evaluated for downstream experimental validation. The biological activity test showed that peptide 3 successfully exhibited a 36.2% inhibition rate against DPP-IV <i>in vitro</i>. These findings indicate that both peptides 3 and 10 are promising DPP-IV inhibitor candidates. 2026-09-18T00:00:00Z Dataset Dataset 10.1021/acsomega.6c08022.s001 https://figshare.com/articles/dataset/Discovery_of_Novel_Peptides_as_DPP-IV_Inhibitors_In_Silico_Screening_Molecular_Dynamics_Simulations_and_Preliminary_In_Vitro_Evaluation/33941183 CC BY-NC 4.0