Lipid vector for the delivery of peptides towards intracellular pharmacological targets.
The ability of single-chain lipopeptides to gain access to cellular compartments other than those related to degradation/recycling was first deduced from their capacity to deliver peptide antigens into MHC-class I loading mechanisms. The ability of lipopeptides to escape complete endosome degradation was further illustrated by the selective inhibition of different protein kinase C isoenzymes and, more recently, the presentation of agonistic activity towards the interferon gamma receptor. Taken together, several independent results indicate that modification of a peptide by a single lipid chain confers upon it intracellular trafficking properties that can be used to deliver functional cargo peptides into living cells; the endoplasmic reticulum, cytosolic protease activity, sites of kinase activity, or even the signalling pathway associated with cytokine stimulation, all appear accessible to peptide modified by a single lipidic moiety. In this context, the interferon gamma receptor can be considered as a very discriminative pharmacological model, useful for the comparative evaluation of the cellular delivery of lipopeptides, as it allows the unambiguous tracking of their intact delivery into a wide range of cellular compartments. This model is now being used to probe the influence of the nature of the lipid moiety on the trafficking properties of lipopeptides.
Gras-Masse
Hélène
H
Sedac-Therapeutics, Parc Eurasanté Lille-Métropole, 85 Rue Nelson Mandela, 59120 Loos, France. helen.gras@sedac-therapeutics.com
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D016503:Drug Delivery Systems / Q000639:trends; D005544:Forecasting; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008055:Lipids; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics
D008055:Lipids; D010455:Peptides; D007371:Interferon-gamma