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Chapter 1 Piercing Lipid Bilayers with Peptides

Abstract:

Disruption of the permeability barrier of biological membranes is one of the mechanisms exploited by nature to allow the physiological or pathological chemical communication between otherwise isolated like compartments. Despite the molecular complexity of these membranes, the lipid bilayer backbone is the permeability guardian, and therefore the universal target of numerous peptides and small proteins that act as perfect weapons. This pathway of cell-life interference is primarily used by the peptides forming part of the innate host defence against pathogens, some of which are exploited as antibiotics in ectopic infection treatments. Similarly, the phage holins, naturally tailored for allowing the release of the phage progeny at the last stage of the lytic cycle, have their application in biotechnological contention and dairy industry. The necessity to modify and regulate the genome and transcriptome of living organism has demanded the access to cell interior without damage. The knowledge accumulated from the peptide-membrane interaction field has allowed the rational "de novo" design of novel peptide sequences that either alone, in combination or in tandem incorporate the capacity to produce the non-toxic membrane permeation events required for efficient gene transfer. RAWA, a 23 amino-acid peptide, serves as a paradigm of this synthetic approach. © 2007 Elsevier Inc. All rights reserved.