ABSTRACT
Introduction: The development of multidrug-resistant strains of bacteria resulting from prolonged treatment with conventional antibiotics has necessitated the need for continuous research for better antibiotic strategies. One of these alternatives is evolutionary antimicrobial peptides also known as host-defense peptides (HDPs). HDPs are an integral part of the innate defense system in multicellular eukaryotes. Although HDPs can largely circumvent the persistent problem of antibiotic resistance due to their bacteriolytic membrane mechanism, they have some drawbacks including a low activity profile and protease instability. AApeptides have recently been introduced as a new class of peptidomimetics with resistance to proteolysis, improved activity profile, and limitless possibilities for structural diversity. Furthermore, they have shown excellent antimicrobial activity.
Areas covered: This review updates the reader on the latest developments of antimicrobial AApeptides, the various derivatizations, and their development for antimicrobial applications. The most recent findings on the heterogeneous γ-AA backbone are also outlined.
Expert opinion: AApeptides have found diverse applications in antimicrobial studies. AApeptides are believed to exhibit bactericidal properties by imitating the membranolytic action of HDPs. They have shown broad-spectrum antimicrobial activity and are active against medicinally relevant drug-resistant pathogens. AApeptides and their derivatives could gain therapeutic relevance in the design and development of antibiotic agents.
Article highlights
The rising rate of antibiotic resistance is a menace to global health due to unchecked use of antibiotics. Multidrug-resistant bacterial strains have caused acute infections since they have become unresponsive to most traditional antibiotics.
Host-defense peptides (HDPs) hold promise for the development of next-generation antibiotics since they can largely overcome obstacles of drug resistance; however, they have their own drawbacks that limit their clinical applications including poor bioavailability, potential immunogenicity, and high cost of production.
AApeptides is a new peptidomimetic scaffold which have found great applications in drug discovery and medicinal chemistry as a result of the derivatization potential of their facile backbone.
AApeptides mostly showed broad-spectrum antimicrobial activity due to their intrinsic ability to adopt global amphipathic conformations upon interaction with bacterial membrane, and mimic HDP in their mechanism of action. They kill pathogenic bacteria by membrane permeation and disruption.
Secondary structure alone does not determine antimicrobial activity. Length of peptides, nature of functional groups, and a good balance of cationic charge and hydrophobicity are all important factors for antimicrobial AApeptides design.
Declaration of Interest
The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.