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Cellular and Molecular Life Sciences

, Volume 68, Issue 13, pp 2255–2266 | Cite as

Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches

  • Andrea Giuliani
  • Andrea C. RinaldiEmail author
Multi-author review

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.

Keywords

Antimicrobial peptides Antimicrobial polymers Synthetic approaches Membrane-active Dendrimeric peptides Lipopeptides 

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

Notes

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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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Spider Biotech S.r.lColleretto GiacosaItaly
  2. 2.Department of Biomedical Sciences and TechnologiesUniversity of CagliariMonserratoItaly

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