2. Academic Validation
  3. Rationally designed small peptides targeting DPP-4: Identification of potent anti-diabetic agents

Rationally designed small peptides targeting DPP-4: Identification of potent anti-diabetic agents

  • Bioorg Chem. 2025 Aug:163:108781. doi: 10.1016/j.bioorg.2025.108781.
Sombir Jaglan 1,  Palwinder Singh 2,  Sheetal Vermani 1,  Varinder Kaur 1,  Sarabjit Kaur 3,  Abdulkadir Abdu 3
Affiliations

Affiliations

  • 1 Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.
  • 2 Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India. Electronic address: palwinder_singh_2000@yahoo.com.
  • 3 Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India.
PMID: 40700924 DOI: 10.1016/j.bioorg.2025.108781
Abstract

DPP-4 inhibition is a pioneering strategy to subdue type 2 diabetes. In this context, we designed and synthesized small peptide-based DPP-4 inhibitors. Eighteen peptides were synthesized, and their inhibition activity was determined. Compound 8 emerged as the most potent DPP-4 Inhibitor (IC50 0.12 nM) with desirable drug likeness properties including solubility, plasma stability, kinetic study, and ADME properties. The in vivo anti-diabetic potency was evaluated in a diabetic model of STZ/NA-induced Wistar rats. Compound 8 not only lined up glucose levels to normal but also improved serum's lipid parameters, liver Enzymes, and renal parameters at medium (20 mg/kg) and high doses (40 mg/kg). Further histopathological analysis of kidney and pancreas tissue shows its curative effect. Compound 8 exhibits selectivity for DPP-4 as binding energy computed by post-dynamic analysis MM-GBSA for compound 8 complex in DPP-4 is almost twofold as of DPP-8 and DPP-9.

Keywords

Dipeptidyl peptidase-4; Drug-likeness; Glucose; Histopathology; Molecular modelling; Peptides; Type 2 diabetes mellitus.

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