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Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches

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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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Abbreviations

AMP:

Antimicrobial peptide

MAP:

Multiple antigenic peptide

LPS:

Lipopolysaccharide

LTA:

Lipoteichoic acid

OAK:

Oligoacyllysine

PEM:

Protein epitope mimetic

ROMP:

Ring-opening metathesis polymerization

SMAMP:

Synthetic mimic of antimicrobial peptides

VV:

Vaccinia virus

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Conflict of interest

One of the authors declares competing financial interests. Andrea Giuliani is an executive board member and minor shareholder of Spider Biotech S.r.l. (www.spiderbiotech.com), which is developing peptide-based anti-infectives.

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Authors and Affiliations

  1. Spider Biotech S.r.l, 10010, Colleretto Giacosa, TO, Italy

    Andrea Giuliani

  2. Department of Biomedical Sciences and Technologies, University of Cagliari, 09042, Monserrato, CA, Italy

    Andrea C. Rinaldi

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  1. Andrea Giuliani
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  2. Andrea C. Rinaldi
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Correspondence to Andrea C. Rinaldi.

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Giuliani, A., Rinaldi, A.C. Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches. Cell. Mol. Life Sci. 68, 2255–2266 (2011). https://doi.org/10.1007/s00018-011-0717-3

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  • DOI: https://doi.org/10.1007/s00018-011-0717-3

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