Attaching histidine-tagged peptides and proteins to lipid-based carriers through use of metal-ion-chelating lipids.
The therapeutic potential of selected peptides and proteins is enormous, with applications ranging from use as therapeutic vaccines, as modulators of intracellular signaling pathways and as highly selective agents capable of recognizing unique extracellular targets. We have been pursuing development of hybrid lipid-based carrier formulations designed to take advantage of the therapeutic benefits of peptides selected for their ability to act in a complementary fashion with the carrier system. In this regard, it is critical to have simple and versatile methods to promote and control the binding of diverse peptides to a broad range of carrier formulations. As demonstrated here, recombinant proteins and synthetic peptides containing poly-histidine residues (4 to 10) can be specifically bound to liposomes containing a metal-ion-chelating lipid, DOGS-NTA-Ni. The potential of this approach is demonstrated using two functional peptides, AntpHD-Cw3 (applications for vaccine production) and AHNP (specificity for Her-2 expressing cells).
Chikh
Ghania G
GG
Department of Advanced Therapeutics, British Columbia Cancer Research Center, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3.
Li
Wai Ming
WM
Schutze-Redelmeier
Marie-Paule
MP
Meunier
Jean-Claude
JC
Bally
Marcel B
MB
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008670:Metals / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
D002614:Chelating Agents; D008055:Lipids; D008081:Liposomes; D008670:Metals; D010455:Peptides; D011506:Proteins; D006639:Histidine