Strategies in translating the therapeutic potentials of host defense peptides

Ting, Darren Shu Jeng, Beuerman, Roger W., Dua, Harminder S., Lakshminarayanan, Rajamani and Mohammed, Imran ORCID: https://orcid.org/0000-0002-8412-0768 2020. Strategies in translating the therapeutic potentials of host defense peptides. Frontiers in Immunology 11 , 983. 10.3389/fimmu.2020.00983

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Abstract

Abstract The golden era of antibiotics, heralded by the discovery of penicillin, has long been challenged by the emergence of antimicrobial resistance (AMR). Host defense peptides (HDPs), previously known as antimicrobial peptides, are emerging as a group of promising antimicrobial candidates for combatting AMR due to their rapid and unique antimicrobial action. Decades of research have advanced our understanding of the relationship between the physicochemical properties of HDPs and their underlying antimicrobial and non-antimicrobial functions, including immunomodulatory, anti-biofilm, and wound healing properties. However, the mission of translating novel HDP-derived molecules from bench to bedside has yet to be fully accomplished, primarily attributed to their intricate structure-activity relationship, toxicity, instability in host and microbial environment, lack of correlation between in vitro and in vivo efficacies, and dwindling interest from large pharmaceutical companies. Based on our previous experience and the expanding knowledge gleaned from the literature, this review aims to summarize the novel strategies that have been employed to enhance the antimicrobial efficacy, proteolytic stability, and cell selectivity, which are all crucial factors for bench-to-bedside translation of HDP-based treatment. Strategies such as residues substitution with natural and/or unnatural amino acids, hybridization, L-to-D heterochiral isomerization, C- and N-terminal modification, cyclization, incorporation with nanoparticles, and “smart design” using artificial intelligence technology, will be discussed. We also provide an overview of HDP-based treatment that are currently in the development pipeline. © Copyright © 2020 Ting, Beuerman, Dua, Lakshminarayanan and Mohammed.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences
Publisher:	Frontiers Media
ISBN:	16643224
ISSN:	1664-3224
Date of Acceptance:	27 April 2020
Last Modified:	01 Jun 2023 16:37
URI:	https://orca.cardiff.ac.uk/id/eprint/152707

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