Fusogenic peptide

Afonin S, Dur UHN, Glaser RW, Ulrich AS (2004) Boomerang -like insertion of a fusogenic peptide in a lipid membrane revealed by solid-state F-19 NMR. Magn Reson Chem 42 195-203... 

Fusogenic peptides, derived from viral sources, are particularly well characterized (107 111). The amphipathic peptide from the A-terminal region of the hemagglutinin (HA)-2 subunit of HA was one of the first such peptides described, and, subsequently, a range of influenza-derived peptides... 

Figure 3 Endosomal escape assisted by fusogenic peptides. These peptides assist the release of DNA from the endosome, avoiding degradative damage from the binding with the lysosome.

A synthetic peptide has been designed to mimic the effects of viral fusogenic properties (114,115). It consists of 30 amino acids with the major repeat of Glu-Ala-Leu-Ala so, it is referred to as a GALA peptide. It undergoes a conversion from an aperiodic conformation at neutral pH and becomes an amphipathic alpha helix at pH 5. In the more acidic environment, the peptide interacts with lipid bilayers (114,115). GALA has been incorporated into transferrin-targeted liposome, with the effect of significantly... 

Vaysse L, Burgelin I, Merlio JP, et al. Improved transfection using epithelial cell line-selected ligands and fusogenic peptides. Biochim Biophys Acta 2000 1475(3) 369-376. 

Wagner E, Plank C, Zatloukal K, et al. Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes toward a synthetic virus-like gene-transfer vehicle. Proc Natl Acad Sci USA 1992 89(17) 7934-7938. 

Kakudo T, Chaki S, Futaki S, et al. Transferrin-modified liposomes equipped with a pH-sensitive fusogenic peptide an artificial viral-like delivery system. Biochemistry 2004 43(19) 5618-5628. 

Bongartz, J.P., Aubertin, A.M., Milhaud, P.G., Lebleu, B. (1994). Improved biological activity of antisense oligonucleotides conjugated to a fusogenic peptide. Nucleic Acids Res., 22, 4681 1688. 

The objective of this chapter is to present an overview of peptide-based gene delivery systems. Some excellent reviews have been written recently on this topic, so we shall only do a summary of fusogenic peptides and then we wih present our recent data. We will particularly focus on the recent progress made concerning low molecular peptide-based gene delivery systems. We wih also attempt to make readers aware of the conceptual and experimental aspects of peptide-based gene delivery system design. 

These anionic peptides can be linked covalently to polylysine conjugates, but that may cause a decrease of their fusogenic features once the polyplexes are formed. For instance, we have found impairment in permeabilization of the plasma membrane upon couphng E5CA to bovine serum albumin (Midoux et al., 1995). 

Table 16.1 Fusogenic glutamic-acid rich peptides...

DBS and NLS stand for DNA binding signal and nuclear localization signal, respectively. Helper indicates that the transfection is efficient in the presence of additives for the cytosolic translocation. Chlo and lipo are chloroquine and cationic lipids, respectively. JTS-1 and HA are fusogenic peptides listed in Table 1. 

DNA binding moiety has been synthesized and evaluated as a receptor-mediated gene delivery system. The system was able to transfect about 30% of corneal endothelial cells of rabbit, pig and human in the presence of chloroquine (Shewring et al., 1997). Associated with the fusogenic peptide of influenza, this peptide transfected 25-30% of primary cultures of vascular smooth muscle cells of man, rabbit and rat (Collins et al., 2000 Li et al., 2000). The molossin-based gene delivery system represents an interesting system in transplantation because the molossin peptide does not bind to vascular endothelium and pancreatic islets. 

Glaser, R.W., Grime, M., Wandelt, C. and Ulrich, A.S. (1999) Structure analysis of a fusogenic peptide sequence from the Sea Urchin fertilization protein binding. Biochemistry, 38,2560-2569. 

Kichler, A., Freulon, I., Boutin, V., Mayer, R., Monsigny, M. and Midoux, P. (1999) Glycofection in the presence of anionic fusogenic peptides a study of the parameters affecting the peptide-mediated enhancement of the transfection efficiency. J. Gene Med., 1, 134-143. 

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