Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Bungarus multicinctus: Simulated Gastrointestinal Digestion, Identification and Antihypertensive Mechanism

TL;DR

This study discovers three new peptides from a snake species that can inhibit an enzyme linked to high blood pressure, offering potential for safer treatments.

Contribution

Identification of three novel ACE-inhibitory peptides from Bungarus multicinctus with antihypertensive potential.

Findings

The <5 kDa fraction showed 79% ACE inhibition at 1 mg/mL with good stability.

Peptides PPSPPRW, WGFTKF, and PSLFPPRL bind strongly to ACE via hydrogen and hydrophobic interactions.

Peptides demonstrated acceptable cell viability at low concentrations, suggesting preliminary safety.

Abstract

Background/Objectives: Hypertension represents a leading contributor to cardiovascular disorders and premature mortality. Given the pervasive nature of adverse effects associated with current angiotensin-converting enzyme inhibitors (ACEIs), there is a significant interest in identifying novel bioactive lead compounds from natural sources. This study identifies, for the first time, three novel angiotensin-converting enzyme (ACE) inhibitory peptides released from Bungarus multicinctus (BM) via simulated gastrointestinal digestion (SGD). Methods: Active fractions were enriched by ultrafiltration and subjected to stability assessment. The peptide sequences were then determined using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and bioinformatics tools, followed by chemical synthesis. Finally, the inhibitory mechanism was investigated using kinetic analysis and molecular docking. Results: The intestinal digest exhibited potent ACE inhibition, with the <5 kDa fraction achieving 79% inhibition at 1 mg/mL and demonstrating favorable stability under varying temperatures, pH, and ionic strengths. Molecular docking revealed strong binding (affinity < −9.9 kcal/mol) of the peptides PPSPPRW, WGFTKF, and PSLFPPRL to key ACE residues—Tyr523, His513, and Arg522—via hydrogen and hydrophobic interactions. Enzyme kinetics characterized PPSPPRW and WGFTKF as competitive inhibitors, and PSLFPPRL as mixed type. The peptides demonstrated acceptable cell viability at lower concentrations, establishing a preliminary safety window for therapeutic application. Conclusions: These findings establish BM as a valuable source of stable, bioactive ACE-inhibitory peptides (ACEIPs) acting as promising lead compounds for antihypertensive therapies.

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