The search for efficient antimicrobial
therapies that can alleviate suffering caused by
infections from resistant bacteria is more urgent than ever before.
Infections caused by multi-resistant pathogens represent a significant and increasing burden to healthcare and society and researcher are investigating new classes of bioactive compounds to slow down this development.
Antimicrobial peptides from the innate immune system represent one promising class that offers a potential
solution to the antibiotic resistance problem due to their mode of action on the microbial membranes. However, challenges associated with pharmacokinetics, bioavailability and off-target toxicity are slowing down the advancement and use of innate defensive
peptides. Improving the therapeutic properties of these
peptides is a strategy for reducing the clinical limitations and synthetic mimics of
antimicrobial peptides are emerging as a promising class of molecules for a variety of antimicrobial applications. These compounds can be made significantly shorter while maintaining, or even improving antimicrobial properties, and several downsized synthetic mimics are now in clinical development for a range of
infectious diseases. A variety of strategies can be employed to prepare these small compounds and this review describes the different compounds developed to date by adhering to a minimum pharmacophore based on an amphiphilic balance between cationic charge and hydrophobicity. These compounds can be made as small as
dipeptides, circumventing the need for large compounds with elaborate three-dimensional structures to generate simplified and potent antimicrobial mimics for a range of medical applications. This review highlight key and recent development in the field of small
antimicrobial peptide mimics as a promising class of antimicrobials, illustrating just how small you can go.