The biological role of charge distribution in linear antimicrobial peptides

ABSTRACT

Introduction

Antimicrobial peptides (AMP) have received particular attention due to their capacity to kill bacteria. Although much is known about them, peptides are currently being further researched. A large number of AMPs have been discovered, but only a few have been approved for topical use, due to their promiscuity and other challenges, which need to be overcome.

Areas covered

AMPs are diverse in structure. Consequently, they have varied action mechanisms when targeting microorganisms or eukaryotic cells. Herein, the authors focus on linear peptides, particularly those that are alpha-helical structured, and examine how their charge distribution and hydrophobic amino acids could modulate their biological activity.

Expert opinion

The world currently needs urgent solutions to the infective problems caused by resistant pathogens. In order to start the race for antimicrobial development from the charge distribution viewpoint, bioinformatic tools will be necessary. Currently, there is no software available that allows to discriminate charge distribution in AMPs and predicts the biological effects of this event. Furthermore, there is no software available that predicts the side-chain length of residues and its role in biological functions. More specialized software is necessary

KEYWORDS:

• Antimicrobial peptides
• AMP features
• peptide/membrane interaction
• charge distribution

Article highlights

• The advent of new diseases caused by microorganisms is putting a major burden on health-care systems, including those that are resistant to the currently available medicines.

• The biological activity of AMPs is modulated by charge distribution

• Charge type (aspartic acid, glutamic acid, arginine, lysine, or amidation) plays a central role in peptide activity.

• Hydrophobic amino acids can make it easier for site-directed peptides to reach the objective.

• Computational analysis of charge distribution in AMPs could facilitate the development of promising drugs.

This box summarizes key points contained in the article.

Declaration of interest

HM Duque is supported by a grant from the CNPq, grant number 150911/2022-0. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17460441.2023.2173736

Additional information

Funding

The authors are supported by the Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia (FUNDECT), the Fundação de Apoio a Pesquisa do Distrito Federal (FAPDF), the Coordination for the Improvement of Higher Education, Brazil (CAPES) and the National Council for Scientific and Technological Development (CNPq).