1-palmitoyl-2-oleoylphosphatidylcholine and HIV-Infections

T-20 (also known as enfuvirtide) is a fusion inhibitor peptide known to have some effectiveness in the control of progression of HIV infection by inhibiting the fusion of the HIV envelope with the target cell membrane. Recent results indicate that T-20 is able to interact with membranes in the liquid disordered state but not with membranes in an ordered state, which could be linked to its effectiveness. A detailed molecular picture of the interaction of these molecules with membranes is still lacking. To this effect, extensive molecular dynamics simulations (100 ns) were carried out to investigate the interaction between T-20 and bilayers of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and POPC/cholesterol (1:1). Membrane properties such as area/lipid, density profiles, order parameters and membrane thickness were studied. It was observed that T-20 has the ability to interact to different extents with both model membranes in this study and that peptide interaction with the bilayer surface has a local effect on membrane structure. The formation of hydrogen bonding between certain peptide residues and the POPC phosphate group was observed. However, T-20 showed a more limited extent of interaction with model membranes when compared with other, more efficient, peptides (such as T-1249). This effect is most notable in POPC/Chol membranes in which interaction is especially weak, owing to less peptide residues acting as H bond donors to POPC and virtually no H bonds being formed between T-20 and cholesterol. This lower ability to interact with membranes is probably correlated with its smaller inhibitory efficiency.

Topics: Cholesterol; Enfuvirtide; HIV; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; Humans; Lipid Bilayers; Molecular Dynamics Simulation; Peptide Fragments; Phosphatidylcholines

2F5, a monoclonal antibody that neutralizes HIV-1 primary isolates, recognizes an epitope in the membrane proximal region of the glycoprotein gp41 ectodomain. It is believed that binding to the viral membrane is a step in the antibody mode of action, as usual in ligand membrane receptor interactions. We investigated the interaction of 2F5 with membrane model systems, namely large unilamellar vesicles, by means of fluorescence techniques. There were no significant interactions of 2F5 with model viral membranes or with model target cell membranes. Thus, the usual three-step 'membrane catalysis' method is not followed by 2F5 in its mode of action.

Topics: Amino Acids, Aromatic; Antibodies, Monoclonal; Epitopes; Fluorescent Dyes; Fluorometry; HIV Infections; HIV-1; Humans; Immunotherapy; Membranes; Phosphatidylcholines; Pyridinium Compounds