Author: Shai, Y.

Source: Current Pharmaceutical Design, Volume 8, Number 9, 1 April 2002 , pp. 715-725(11)

Publisher: Bentham Science Publishers

Abstract:

Antimicrobial peptides are a large group of gene-encoded, net positively charged polypeptides, produced by living organisms of all types including human and plants. They are mobilized shortly after infection as part of the innate immunity of these species and act rapidly to neutralize a broad range of microbes. Nowadays, thousands of native and de-novo designed antimicrobial peptides are available. They vary considerably in length, composition, charge and secondary structure. Despite these variations most antimicrobial peptides use a similar target, which is the bacterial phospholipid membrane. Many of them use a common general mechanism, the ”carpet“mechanism, in which they accumulate on the bacterial membrane up to a threshold concentration, and then effect membrane permeation / disintegration. However, the structure of the permeation pathway may vary for different peptides and may include channel aggregates, toroidal pores or channels. Target specificity is determined by the negatively charged bacterial membrane, the net positive charge of the peptide, its hydrophobicity, oligomeric state in solution and in the membrane, and the stability of its secondary structure. A novel group of non hemolytic antimicrobial peptides were derived from diastereomers (containing D- and L-amino acids) of lytic peptides based on parameters required by the carpet mechanism. Because these disastereomers exhibit several advantages over their all-L amino acid counterparts, they have a potential to be developed for therapeutic use both in vitro and in vivo.

Keywords: antibacterial peptides; diastereomer; cell lysis; lytic peptide; innate immunity; peptide lipid interaction

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612023395367

Publication date: 2002-04-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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