INTERACTION OF RECOMBINANT INTERLEUKIN-2 WITH LIPOSOMAL BILAYERS

Liposomes have been employed as a delivery system for recombinant inte rleukin-2 (rIL-2) in cancer immunotherapy. in this study the effects o f the rIL-2-bilayer interaction on protein structure were investigated . It was shown that rIL-2 adsorbs to liposomal membranes when added to preformed liposomes. Polarized fluorescence decay studies showed that the single tryptophan in ''native'' rIL-2 has a relatively large moti onal freedom, although iodide quenching of this residue's fluorescence was relatively ineffective. However, adsorption of rIL-2 to liposomes alters this situation dramatically-fluorescence intensity increased 2 -fold and the residue became more susceptible to iodide quenching. At the same time, the average fluorescence lifetime of the fluorophore is extended. interestingly, circular dichroism studies showed that no ma jor conformational changes occurred in rIL-2's secondary structure upo n adsorption. These observations support the hypothesis that intramole cular quenching takes place in the native rIL-2 molecule, which is abr ogated upon adsorption to the liposomal membrane, resulting in a highe r fluorescence intensity. Fluorescence anisotropy decay experiments in dicate that the protein forms self-aggregates under the [ow-ionic stre ngth conditions used, confirming the earlier observations on the tende ncy or the protein to precipitate in salt-containing media.