The ability of several classes of polyoxometalates to inhibit the interaction between HIV-1 gp120 and CD4 was assessed. No clear relationship was found between binding inhibition and the negative charge density on the anion portion of the polyoxometalate. However, a weak correlation was found with molecular size. There was a molecular weight threshold of 3800 g mol-1 above which no significant increase in potency was gained; the binding inhibition was nearly quantitative above this molecular weight.
References
1.
ArthosJ.DeenK.C.ChaikinM.A.FornwaldJ.A.SatheG.SattentauQ.J.ClaphamP.R.WeissR.A.McDougalJ.S.PietropaoloC.AxelR.TrunehA.MaddonP.J., and SweetR. (1989) Identification of the residues in human CD4 critical for the binding of HIV. Cell57: 469–481.
2.
BabaM.ScholsD.De ClercqE.PauwelsR.NagyM.Gyorgi-EdelenylJ.LowM., and GorogS. (1990) Novel sulfated polymers as highly potent and selective inhibitors of human immunodeficiency virus replication and giant cell formation. Antimicrob Agents Chemother34: 184–188.
3.
BagasraO., and LischnerH.W. (1988) Activity of dextran sulfate and other polyanionic polysaccharides against human immunodeficiency virus. J Infect Dis158: 1084.
4.
BerryJ.P., and GalleP. (1990) Subcellular localization of HPA-23 in different rat organs: Electron microprobe study. Exp Mol Path53: 255–264.
5.
BlaseckiJ.W. (1994) Of therapy, toxicity and tungstates: The anti-retroviral pharmacology of polyoxometalates. In: Polyoxometalates: From Platonic Solids to Anti-retroviral Activity.PopeM.T.MüllerA. (eds). Dordrecht: Kluwer Academic Publishers, pp. 373–385.
6.
ChouJ., and ChouT.-C. (1985) Dose-effect analysis with microcomputers: Quantitation of ED50, LD50, synergism, antagonism, low-dose risk, receptor binding, and enzyme kinetics. In: A computer software for Apple II series and IBM-PC and instruction manual Elsevier-Biosoft.Cambridge, UK: Elsevier Science Publishers.
7.
ClayeteP., and DormontD. (1994) Polyoxometalates in AIDS Therapy. In: Polyoxometalates: From Platonic Solids to Antiretroviral Activity.PopeM.T.MüllerA. (eds). Dordrecht: Kluwer Academic Publishers, pp. 387–399.
8.
DalgleishA.G.BeverlyP.C.L.ClaphamP.R.CrawfordD.H.GreavesM.F., and WeissR.A. (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature312: 763.
9.
HillC.L.HartnupM.FarajM.WeeksM.Prosser-McCarthaC.M.BrownR.B.SchinaziR.F.SommadossiJ.-P. (1990a) Polyoxometalates as inorganic anti-HIV-1 compounds. Structure-activity relationships. In: Advances in Chemotherapy of AIDS, Pharmacology and Therapeutics.DiasioR.SommadossiJ.-P. (eds). New York: Pergamon, pp. 33–41.
10.
HillC.WeeksM., and SchinaziR.F. (1990b) Anti-HIV-1 activity, toxicity, and stability studies of representative structural families of polyoxometalates. J Med Chem33: 2767.
11.
HillC.L.KimG.-S.Prosser-McCarthaC.M., and JuddD. (1994) Polyoxometalates in catalytic selective homogeneous oxygenation and anti-HIV chemotherapy. In: Polyoxometalates: From Platonic Solids to Anti-retroviral Activity.PopeM.T.MüllerA. (eds). Dordrecht: Kluwer Academic Publishers, pp. 359–371.
12.
IkedaS.NishiyaS.YamamotoA.YamaseT.NishimureC., and De ClercqE. (1994) Antiviral activity of a keggin polyoxotungstate PM-19 against herpes simplex virus in mice. Antiviral Chem Chemother5: 47–50.
13.
KimG.-S.JuddD.A.HillC.L., and SchinaziR.F. (1994) Synthesis, characterization, and biological activity of a new potent class of anti-HIV agents, the peroxoniobium substituted heteropolytungstates. J Med Chem37: 816–820.
14.
KlatzmannD.ChampagneL.ChamaretS.GruestJ.GuetardD.HercendT.GluckmanJ.C., and MontagnierL. (1984) T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature312: 767.
15.
LedermanS.GulickR., and ChessL. (1989) Dextran sulfate and heparin interact with CD4 molecules to inhibit the binding of coat protein (gp120) of HIV. J Immunol143: 1149–1154.
16.
McDougalJ.S.KennedyM.S.SlighJ.M.CortS.P.MawleA., and NicholsonJ.K. (1986a) Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110 K viral protein and the T4 molecule. Science231: 382.
17.
McDougalJ.S.MaddonP.J.DalgleishA.G.ClaphamP.R.LittmanD.R.GodfreyM.MaddonD.E.ChessL.WeissR.A., and AxelR. (1986b) The T4 glycoprotein is a cell-surface receptor for the AIDS virus. Cold Spring Harbor Symp Quant Biol51: 703.
18.
MitsuyaH.LooneyD.J.KunoS.UenoR.Wong-StaalF., and BroderS. (1988) Dextran sulfate suppression in viruses in the HIV family: Inhibition of virion binding to CD4+ cells. Science240: 646–649.
19.
MoscickiR.A.AmentoE.P.KraneS.M.KurnickJ.T., and ColvinR.B. (1983) Modulation of surface antigens of a human monocyte cell, U937, during incubation with T lymphocyte conditioned medium: detection of T4 antigen and its presence on normal blood monocytes. J Immunol131: 743.
20.
NiL.BoudinotF.D.BoudinotS.G.HensonG.W.BossardG.E.MartellucciS.A.AshP.W.FrickerS.P.DarkesM.C.TheobaldB.R.C.HillC.L., and SchinaziR.F. (1994) Pharmacokinetics of antiviral polyoxometalates in rats. Antimicrob Agents Chemother38: 504–510.
21.
ParishC.R.McPhunV., and WarrenH.S. (1988) Is a natural ligand of the T lymphocyte CD4 molecule a sulfated carbohydrate?J Immunol141: 3498.
22.
ParishC.R.LowL.WarrenH.S., and CunninghamA.L. (1990) A polyanion binding site on the CD4 molecule. Proximity to the HIV-gp120 binding region. J Immunol145: 1188–1195.
23.
PopeM.T., and MüllerA. (1991) Polyoxometalate chemistry: An old field with new dimensions in several disciplines. Angew Chem Int Ed Eng30: 34–48.
24.
PopeM.T., and MüllerA. (1994) Polyoxometalates: From Platonic Solids to Anti-retroviral Activity.Dordrecht: Kluwer Academic Publishers.
25.
SchinaziR.F.HillC.L.LiottaD.C.ChuC.K.WudlF., and SommadossiJ.-P. (1994) Sights and insights into novel derivatized C60 fullerenes, polyoxometalates, and enantiomeric nucleoside antiviral agents. In: Vlth International Antiviral Symposium, Nice, France, June 7-10, 1994.
26.
ScholsD.BabaM.PauwelsR., and De ClercqE. (1989a) Flow cytometric method to demonstrate whether anti-HIV-1 agents inhibit virion binding to T4+ cells. J Aids2: 10–15.
27.
ScholsD.BabaM.PauwelsR.DesmyterJ., and De ClercqE. (1989b) Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 receptor. Proc Natl Acad Sci USA86: 3322–3326.
28.
ScholsD.De ClercqE.BalzariniJ.BabaM.WiturouwM.HosoyaM.AndreiG.SnoeckR.NeytsR.PauwelsR.NagyM.Gyorgi-EdelenylJ.MachovichJ.HorvathJ.LowM., and GorogS. (1990) Sulfated polymers are potent and selective inhibitors of various envelope viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatis virus, respiratory syncytial virus, and toga-, arena-, and retroviruses. Antiviral Chem Chemother1: 233–240.
29.
ScholsD.PauwelsR.WitvrouwM.DesmyterJ., and De ClercqE. (1992) Differential activity of polyanionic compounds and castanospermine against HIV replication and HIV-induced syncytium formation depending on virus strain and cell type. Antiviral Chem Chemother3: 23–30.
30.
TerhorstC.A.van AgthovenE.ReinherzE., and SchlossmanS. (1980) Biochemical analysis of human lymphocyte differentiation antigens T4 and T8. Science209: 520.
31.
ThieleB.BraigH.R.EhmI.KunzeR., and RufB. (1989) Influence of sulfated carbohydrates on the accessibility of CD4 and other CD molecules on the cell surface and implications for human immunodeficiency virus infection. Eur J Immunol19: 1161–1164.
32.
WeaverJ.L.GergeleyP.PineP.S.PatzerE., and AszalosA. (1990) Polyionic compounds selectively alter availability of CD4 receptors for HIV coat protein rgp120. AIDS Res Hum Retroviruses6: 1125–1130.
33.
WeeksM.S.HillC.L., and SchinaziR.F. (1992) Synthesis, characterization and anti-human immunodeficiency virus activity of water soluble salts of polyoxotungstate anions with covalently attached organic groups. J Med Chem35: 1216–1222.
34.
YamamotoN.ScholsD.De ClercqE.DebyserZ.PauwelsR.BalzariniJ.NakashimaH.BabaM.HosoyaM.SnoeckR.NeytsJ.AndreiG.MurrerB.A.TheobaldB.BossardG.HensonG.AbramsM., and PickerD. (1993) Mechanism of anti-human immunodeficiency virus action of polyoxometalates, a class of broad-spectrum antiviral agents. Mol Pharmacol49: 1109–1117.
