Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches |
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Authors: | Andrea?Giuliani Email author" target="_blank">Andrea?C?RinaldiEmail author |
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Institution: | (1) Spider Biotech S.r.l, 10010 Colleretto Giacosa, TO, Italy;(2) Department of Biomedical Sciences and Technologies, University of Cagliari, 09042 Monserrato, CA, Italy; |
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Abstract: | Naturally occurring antimicrobial peptides (AMPs) present several drawbacks that strongly limit their development into therapeutically
valuable antibiotics. These include susceptibility to protease degradation and high costs of manufacture. To overcome these
problems, researchers have tried to develop mimics or peptidomimetics endowed with better properties, while retaining the
basic features of membrane-active natural AMPs such as cationic charge and amphipathic design. Protein epitope mimetics, multimeric
(dendrimeric) peptides, oligoacyllysines, ceragenins, synthetic lipidated peptides, peptoids and other foldamers are some
of the routes explored so far. The synthetic approach has led to compounds that have already entered clinical evaluation for
the treatment of specific conditions, such as Staphylococcus (MRSA) infections. Should these trials be successful, an important proof-of-concept would be established, showing that synthetic
oligomers rather than naturally occurring molecules could bring peptide-based antibiotics to clinical practice and the drug
market for local and systemic treatment of medical conditions associated with multi-drug resistant pathogens. |
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