T-20 and T-1249 HIV fusion inhibitors' structure and conformation in solution: A molecular dynamics study

Journal of Peptide Science

Volumn 14, Issue 4, 2008, Pages 442-447

  Martin Do Canto, António M T ^a   Carvalho, A J Palace ^a   Ramalho, J P Prates ^a   Loura, Luís M S ^a,b  

^a UNIVERSITY OF ÉVORA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

AIDS; Enfurvitlde; HIV fusion inhibitor; Molecular dynamics; Molecular simulations; T 1249; T 20

Indexed keywords

CYTIDINE TRIPHOSPHATE; ENFUVIRTIDE; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; T 1249; WATER;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ALPHA HELIX; ARTICLE; COMPUTER SIMULATION; CONTROLLED STUDY; DRUG CONFORMATION; DRUG DESIGN; DRUG STRUCTURE; EXPERIMENTAL STUDY; MEMBRANE FUSION; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; SOLVENT EFFECT;

AMINO ACID SEQUENCE; COMPUTER SIMULATION; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV-1; HUMANS; MOLECULAR CONFORMATION; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; PROTEIN STRUCTURE, SECONDARY; SOLUTIONS;

EID: 42149132659     PISSN: 10752617     EISSN: 10991387     Source Type: Journal    
DOI: 10.1002/psc.982     Document Type: Article

References (30)

1. Weissenhorn W, Dessen A, Calder LJ, Harrison SC, Skehel JJ, Wiley DC. Structural basis for membrane fusion by enveloped viruses. Mol Membr Biol. 1999; 16: 3-9.
2. Fujii G, Horvath S, Woodward S, Eiserling F, Eisenberg D. A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41. Protein Sci. 1992; 1: 1454-1464.
3. Lawless MK, Barney S, Guthrie KI, Bucy TB, Petteway SR Jr, Merutka G. HIV-1 membrane fusion mechanism: structural studies of the interactions between biologically-active peptides from gp41. Biochemistry 1996; 35: 13697-13708.
4. Colman PM, Lawrence MC. The structural biology of type I viral membrane fusion. Nat. Rev. Mol. Cell Biol. 2003; 4: 309-319.
5. Lasky LA, Nakamura G, Smith DH, Fennie C, Shimasaki C, Patzer E, Berman P, Gregory T, Capon DJ. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell 1987; 50: 975-985.
6. Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup PA, Moore JP, Paxton WA. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996; 381: 667-673.
7. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane. G protein-coupled receptor. Science 1996; 272: 872-877.
8. Kliger Y, Aharoni A, Rapaport D, Jones P, Blumenthal R, Shai Y. Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study. J. Biol. Chem. 1997; 272: 13496-13505.
9. Jiang S, Zhao Q, Debnath AK. Peptide and non-peptide HIV fusion inhibitors. Curr. Pharm. Des. 2002; 8: 563-580.
10. Eron JJ, Gulick RM, Bartlett JA, Merigan T, Arduino R, Kilby JM, Yangco B, Diers A, Drobnes C, DeMasi R, Greenberg M, Melby T, Raskino C, Rusnak P, Zhang Y, Spence R, Miralles GD. Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV. J. Infect. Dis. 2004; 189: 1075-1083.
11. Kilby JM, Hopkins S, Venetta TM, DiMassimo B, Cloud GA. Lee JY, Alldredge L, Hunter E, Lambert D, Bolognesi D, Matthews T, Johnson MR, Nowak MA, Shaw GM, Saag MS. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat. Med. 1998; 4: 1302-1307.
12. Baldwin CE, Sanders RW, Berkhout B. Inhibiting HIV-1 entry with fusion inhibitors. Curr. Med. Chem. 2003; 10: 1633-1642.
13. Cooley LA, Lewin SR. HIV-1 cell entry and advances in viral entry inhibitor therapy. J. Clin. Virol. 2003; 26: 121-132.
14. Kilby JM, Lalezari JP, Eron JJ, Carlson M, Cohen C, Arduino RC, Goodgame JC, Gallant JE, Volberding P, Murphy RL, Valentine F, Saag MS, Nelson EL, Sista PR, Dusek A. The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults. AIDS Res. Hum. Retroviruses 2002: 18: 685-693.
15. Kilby JM, Eron JJ. Novel therapies based on mechanisms of HIV-1 cell entry. N. Engl. J. Med. 2003; 348: 2228-2238.
16. Veiga S, Henriques S, Santos NC, Castanho M. Putative role of membranes in the HIV fusion inhibitor enfuvirtide mode of action at the molecular level. Biochem. J. 2004; 377: 107-110.
17. Veiga AS, Santos NC, Loura LMS, Fedorov A, Castanho MA. HIV fusion inhibitor peptide T-1249 is able to insert or adsorb to lipidic bilayers. Putative correlation with improved efficiency. J. Am. Chem. Soc. 2004; 126: 14758-14763.
18. Thompson MA. ArgusLab 4.0.1. Planaria Software LLC: Seattle, WA, 2004.
19. Berendsen HJC, Postma JPM, van Gunsteren WIT, Hermans J. Interaction models for water in relation to protein hydration. In Intermolecular Forces, Pullman B (ed.). D. Reidel Publishing Company: Dordrecht, 1981; 331-342.
20. Bekker H, Berendsen HJC, Dijkstra EJ, Achterop S, van Drunen R, van der Spoel D, Sijbers A, Keegstra H, Reitsma B, Renardus MFR. GROMACS: A parallel computer for molecular dynamics simulations. In Physics Computing 92, de Groot RA, Nadrchal J (eds). World Scientific: Singapore, 1993.
21. van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC. GROMACS: fast, flexible and free. J. Comp. Chem. 2005; 26: 1701-1718.
22. van Gunsteren WF, Daura X, Mark AE. The GROMOS force field. In Encyclopaedia of Computational Chemistry, Schleyer PvR, Allinger L, Schaefer F (eds), John Wiley and Sons: New York, 1997.
23. Scott WRP, Hunenberger PH, Tironi IG, Mark AE, Billeter SR, Fennen J, Torda AE, Huber T, Kruger P, van Gunsteren WF. The GROMOS biomolecular simulation program package. J. Phys. Chem. A 1999; 103: 3596-3607.
24. Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 1984; 81: 3684-3690.
25. Miyamoto S, Kollman PA. SETTLE: an analytical version of the SHAKE and RATTLE algorithm for rigid water models. J. Comp. Chem. 1992; 13: 952-962.
26. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM. LINCS: A linear constraint solver for molecular simulations. J. Comp. Chem. 1997; 18: 1463-1472.
27. Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 1983; 22: 2577-2637.
28. DwyerJJ, Wilson KL, Davison DK, Freel SA, Seedorff JE, Wring SA, Tvermoes NA, Matthews TJ, Greenberg ML, Delmedico MK. Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 12772-12777.
29. Andrade MA, Chacón P, Merelo, JJ, Morán F. Evaluation of secondary structure of proteins from UV circular dichroism using an unsupervised learning neural network. Prot. Eng. 1993; 6: 383-390.
30. Campbell SM, Crowe SM, Mak J. Virion-associated cholesterol is critical for the maintenance of HIV-1 structure and infectivity. AIDS 2002; 16: 2253-2261.