Exploring the Potential of Bioactive Peptides: From Natural Sources to Therapeutics

Abstract

Bioactive peptides, specific protein fragments with positive health effects, are gaining traction in drug development for advantages like enhanced penetration, low toxicity, and rapid clearance. This comprehensive review navigates the intricate landscape of peptide science, covering discovery to functional characterization. Beginning with a peptidomic exploration of natural sources, the review emphasizes the search for novel peptides. Extraction approaches, including enzymatic hydrolysis, microbial fermentation, and specialized methods for disulfide-linked peptides, are extensively covered. Mass spectrometric analysis techniques for data acquisition and identification, such as liquid chromatography, capillary electrophoresis, untargeted peptide analysis, and bioinformatics, are thoroughly outlined. The exploration of peptide bioactivity incorporates various methodologies, from in vitro assays to in silico techniques, including advanced approaches like phage display and cell-based assays. The review also discusses the structure-activity relationship in the context of antimicrobial peptides (AMPs), ACE-inhibitory peptides (ACEs), and antioxidative peptides (AOPs). Concluding with key findings and future research directions, this interdisciplinary review serves as a comprehensive reference, offering a holistic understanding of peptides and their potential therapeutic applications.

Keywords: bioactivity assays; mass spectrometry; peptidomics; structure–activity relationship; therapeutic peptides.

Figure 1

A representative peptidomics-based workflow for isolation and characterization of novel bioactive peptides from natural sources. Created with BioRender.com (accessed on 12 December 2023).

Figure 2

A few of the common screening approaches for bioactive peptides. (a) Illustrative representation for bead array to identify peptides based on a protein-bead library with photocleavable mass tags; (b) process illustration of phage display involving recombinant antibody (rAB) phage pool for an extensive biased screening of peptides; (c) illustrative representation of reporter gene assay measuring gene expression level in response to an interference with cellular signalling pathway. Created with BioRender.com (accessed on 22 January 2024).

Figure 3

Simplified representation of the mechanism of action of cationic antimicrobial peptides (AMPs) on bacterial cell membrane—cationic AMPs, upon binding to the bacterial cell membrane, cause membrane thinning and disrupt the integrity of the membrane, thus paving the way for the translocation of AMPs into the cell. Created with BioRender.com (accessed on 12 December 2023).