RESUMO
Antimicrobial peptides (AMPs) are considered a promising therapeutic approach against multi-drug resistant microorganisms. Besides their advantages, there are limitations to be overcome so that these molecules can become market competitive. One of the biggest limitations is proteolytic susceptibility, which could be overcome by structural modifications such as cyclization, especially for helix-constraining strategies. Over the years, many helix stabilization techniques have arisen, such as lactam-bridging, triazole-based, N-alkylation and all-hydrocarbon stapling. All-hydrocarbon stapling takes advantage of modified amino acid residues and olefinic cross-linking to constrain peptide helices. Despite being a well-established strategy and presenting efficient stability results, there are different limitations especially related to toxicity. In this review, recent studies on stapled AMPs for antimicrobial usage are explored with the aim of understanding the future of these molecules as putative antimicrobial agents.
RESUMO
Increasing levels of resistance to conventional antibiotics have led to a search for new therapeutic options against bacterial infections. Klebsiella pneumoniae is considered a world health problem due to high levels of mortality associated with resistance to multiple antibiotics. Antimicrobial peptides (AMPs) have showed activity against this bacterium, which makes them a promising alternative in tackling resistance. In this article, we carried out an overview of the recent development of AMPs against K. pneumoniae using different designs and acting by different mechanisms, such as a recently proposed one against capsulated strains. Moreover, we outline AMPs' therapeutic potential when tested in combination with conventional antibiotics and against biofilms. Furthermore, challenges and perspectives for applying AMPs in clinical practice are discussed here.