Conjugation of antimicrobial peptides to enhance therapeutic efficacy

Abstract

The growing prevalence of antimicrobial resistance (AMR) has brought with it a continual increase in the numbers of deaths from multidrug-resistant (MDR) infections. Since the current arsenal of antibiotics has become increasingly ineffective, there exists an urgent need for discovery and development of novel antimicrobials. Antimicrobial peptides (AMPs) are considered to be a promising class of molecules due to their broad-spectrum activities and low resistance rates compared with other types of antibiotics. Since AMPs also often play major roles in elevating the host immune response, the molecules may also be called "host defense peptides." Despite the great promise of AMPs, the majority remain unsuitable for clinical use due to issues of structural instability, degradation by proteases, and/or toxicity to host cells. Moreover, AMP activities in vivo can be influenced by many factors, such as interaction with blood and serum biomolecules, physiological salt concentrations or different pH values. To overcome these limitations, structural modifications can be made to the AMP. Among several modifications, physical and chemical conjugation of AMP to other biomolecules is widely considered an effective strategy. In this review, we discuss structural modification strategies related to conjugation of AMPs and their possible effects on mode of action. The conjugation of fatty acids, glycans, antibiotics, photosensitizers, polymers, nucleic acids, nanoparticles, and immobilization to biomaterials are highlighted.

Keywords: Antimicrobial peptides; Antimicrobial resistance; Conjugation; Multidrug resistant infection; Novel antimicrobials.