HIV Fusion Inhibitor Peptide T-1249 Is Able To Insert or Adsorb to Lipidic Bilayers. Putative Correlation with Improved Efficiency
| Autor: | Nuno Santos, Alexander Fedorov, Miguel Castanho, Aleksandr Fedorov, Luis Loura, Ana Salome Veiga |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Lipid Bilayers Molecular Sequence Data Fluorescence spectrometry Peptide Enfuvirtide Biochemistry Catalysis chemistry.chemical_compound Colloid and Surface Chemistry Fluorescence Resonance Energy Transfer Amino Acid Sequence POPC chemistry.chemical_classification Chromatography Sequence Homology Amino Acid Vesicle technology industry and agriculture Peptide T Membranes Artificial Biological membrane General Chemistry Viral membrane HIV Envelope Protein gp41 Peptide Fragments Kinetics Cholesterol Spectrometry Fluorescence Membrane chemistry Phosphatidylcholines Biophysics Thermodynamics lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of the American Chemical Society. 126:14758-14763 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja0459882 |
| Popis: | T-1249 is a HIV fusion inhibitor peptide under clinical trials. Its interaction with biological membrane models (large unilamellar vesicles) was studied using fluorescence spectroscopy. A gp41 peptide that includes one of the hydrophobic terminals of T-1249 was also studied. Both peptides partition extensively to liquid-crystalline POPC (1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine) (DeltaG = -7.0 kcal/mol and -8.7 kcal/mol, for T-1249 and terminal peptide, respectively) and are located at the interface of the membrane. T-1249 is essentially in a random coil conformation in this lipidic medium, although a small alpha-helix contribution is present. When other lipid compositions are used (DPPC, POPG + POPC, and POPC + cholesterol) (DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and POPG (1-palmitoyl-2-oleyl-sn-glycero-3-[phospho-rac-(1-glycerol)), partition decreases, the most severe effect being the presence of cholesterol. Partition experiments and fluorescence resonance energy transfer analysis show that T-1249 adsorbs to cholesterol-rich membranes. The improved clinical efficiency of T-1249 relative to enfuvirtide (T20) may be related to its bigger partition coefficient and ability to adsorb to rigid lipidic areas on the cell surface, where most receptors are inserted. Moreover, adsorption to the sterol-rich viral membrane helps to increase the local concentration of the inhibitor peptide at the fusion site. |
| Databáze: | OpenAIRE |
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