Antimicrobial Peptides

Antimicrobial peptides (AMPs) are a diverse class of molecules that form a critical component of innate immune defense across virtually all life forms. These peptides typically feature amphipathic structures with cationic and hydrophobic domains that enable them to interact with and disrupt microbial membranes, though many also exhibit intracellular mechanisms of action.

The peptides in this category range from endogenous human defense peptides like LL-37 (the only human cathelicidin) to natural products such as colistin (a last-resort antibiotic against multidrug-resistant Gram-negative bacteria) and daptomycin (an FDA-approved lipopeptide for Gram-positive infections). Research-stage compounds include pexiganan (a synthetic magainin-2 analog that reached Phase 3 trials for diabetic foot ulcers), brilacidin (a defensin-mimetic small molecule), and melittin (the principal component of bee venom, under investigation as an anti-cancer agent via nanoparticle delivery).

Despite decades of research, only a handful of antimicrobial peptides have achieved regulatory approval for systemic use, largely due to challenges with toxicity, serum instability, and manufacturing costs. However, the global rise of antibiotic resistance has renewed interest in AMPs as potential alternatives or adjuncts to conventional antibiotics.