Putative role of membranes in the HIV fusion inhibitor enfuvirtide mode of action at the molecular level.

Partition of the intrinsically fluorescent HIV fusion inhibitor enfuvirtide into lipidic membranes is relatively high (Delta G =6.6 kcal x mol(-1)) and modulated by cholesterol. A shallow position in the lipidic matrix makes it readily available for interaction with gp41. No conformational energetic barrier prevents enfuvirtide from being active in both aqueous solution and lipidic membranes. Lipidic membranes may play a key role in the enfuvirtide biochemical mode of action.

[1]  E Jakobsson,et al.  Combined Monte Carlo and molecular dynamics simulation of fully hydrated dioleyl and palmitoyl-oleyl phosphatidylcholine lipid bilayers. , 1999, Biophysical journal.

[2]  Manuel Prieto,et al.  Quantifying molecular partition into model systems of biomembranes: an emphasis on optical spectroscopic methods. , 2003, Biochimica et biophysica acta.

[3]  L. Mayer,et al.  Vesicles of variable sizes produced by a rapid extrusion procedure. , 1986, Biochimica et biophysica acta.

[4]  Robert B. Gennis,et al.  Biomembranes: Molecular Structure and Function , 1988 .

[5]  M. Prieto,et al.  Interaction of the major epitope region of HIV protein gp41 with membrane model systems. A fluorescence spectroscopy study. , 1998, Biochemistry.

[6]  Luís M. S. Loura,et al.  Resonance energy transfer in a model system of membranes: application to gel and liquid crystalline phases. , 1996, Biophysical journal.

[7]  J. García de la Torre,et al.  Joint determination by Brownian dynamics and fluorescence quenching of the in-depth location profile of biomolecules in membranes. , 2002, Analytical biochemistry.

[8]  S. A. Gallo,et al.  Mode of Action of an Antiviral Peptide from HIV-1 , 2001, The Journal of Biological Chemistry.

[9]  J. Seelig,et al.  Isothermal titration calorimetry for studying interactions between peptides and lipid membranes , 2002 .

[10]  Stephen C. Blacklow,et al.  A trimeric structural domain of the HIV-1 transmembrane glycoprotein , 1995, Nature Structural Biology.

[11]  E. Müller.  Biomembranes, R.B. Gennis, in: Molecular Structure and Function. Series: Springer Advanced Texts in Chemistry, 533 S.. Springer-Verlag, New York-Berlin-Heidelberg-London-Paris-Tokyo (1989), 142 Abb., zahlr. Tab. Preis: DM 98. , 1990 .

[12]  J. Montaner,et al.  Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. , 2003, The New England journal of medicine.

[13]  A. Debnath,et al.  Peptide and non-peptide HIV fusion inhibitors. , 2002, Current pharmaceutical design.