Background: After the era of serendipitous discovery of penicillin and outburst in the discovery and development of highly efficient antibiotics, a surge in resistance against the target specific drugs was observed, primarily due to a combination of selective pressure of antibiotics use and spontaneous mutations. As per the World Health Organization, antibiotic resistance is one of the greatest threats to the mankind.
Objective: Short antimicrobial peptides (SAMPs) can be considered as a viable therapeutic alternative to conventional antibiotics in tackling resistant microbes. The ubiquitous nature of SAMPs combined with their ability to act via non-specific modes of action, high activity against a wide spectrum of drug-sensitive and drug-resistant microbes, and relative insusceptibility against the development of resistance adds to their desirability as new generation antibiotics.
Results: Due to the natural tendency of peptides to get metabolized by proteolytic enzymes, modification of naturally occurring SAMPs is desirable. The modifications can be done either by incorporating unnatural or modified amino acids into the peptide chain or by protecting C and N termini. The characteristic feature of SAMPs is their hydrophobicity and cationicity, which aid in the effective killing of microbes by selectively binding target and lysing the microbial cells with less deleterious effects on the host cells as compared to AMPs and other conventional antibiotics.
Conclusion: Herein, we discussed the arsenal of short peptides and peptidomimetics starting from the smallest unit possible – a dipeptide to a decapeptide along with their activity profiles as antimicrobials. Recently, various SAMPs have paved their ways from in vitro studies to clinical trials, as evident from the most recent patent (EP1951194) on oral hygiene. This step by step growth of SAMPs has restored the hope in peptide-based therapeutics, which may prove an essential tool in eradicating antimicrobial resistance and tackling various microbial infections.