Abstract
Sulfonated distamycin (Suradista) derivatives exhibit anti-HIV-1 activity by inhibiting the binding of the viral envelope glycoprotein gp120 to its receptor (CD4). With the aim to propose a possible binding mode between Suradistas and the CD4 macromolecule, molecular docking experiments, followed by energy minimization of the complexes thus obtained, were performed. Computational results show that ligand binding at the CD4 surface involves two or three positively charged regions of the macromolecule, in agreement with the results of X-ray crystallographic analysis of a ternary complex (CD4/gp120/neutralizing antibody) recently reported in the literature. Our findings account well for the structure–activity relationship found for Suradista compounds.
Similar content being viewed by others
References
Fantini, J. and Sabatier, J.-M., In Fantini, J. and Sabatier, J.-M. (Eds.), HIV Infection in CD4¯ Cells, ESCOM, Leiden, The Netherlands, 1996, pp. V-VI.
Levy, J.A., Microbiol. Rev., 57 (1993) 183.
Miedema, F., Immunodefic. Rev., 3 (1992) 173.
Miedema, F., Meynaard, L., Koot, M., Klein, M.R., Roos, M.T.L., Groenink, L., Fouchier, R.A.M., Van't Wout, A.B., Tersmette, M., Schellekens, P.T.A. and Schuitemaker, H., Immunol. Rev., 140 (1994) 35.
Bour, S., Geleziunas, R. and Wainberg, M.A., Microbiol. Rev., 59 (1995) 63.
Wang, J., Yan, Y., Garrett, T.P.J., Liu, J., Rodgers, D.W., Garlick, R.L., Tarr, G.E., Husain, Y., Reinherz, E.L. and Harrison, S.C., Nature, 348 (1990) 411.
Ryu, S.-E., Kwong, P.D., Truneh, A., Porter, T.G., Arthos, J., Rosenberg, M., Dai, X., Xuong, N., Axel, R., Sweet, R. and Hendrickson, W., Nature, 348 (1990) 419.
Ramurthy, S., Lee, M.S., Nakanishi, H., Shen, R. and Kahn, M., Biol. Med. Chem., 9 (1994) 1007.
Jarvest, R.L., Breen, A.L., Edge, C.M., Chaikin, M.A., Jennings, L.J., Alemseged, T., Sweet, R.W. and Hertzberg, R.P., Biol. Med. Chem. Lett., 3 (1993) 2851.
Broder, C.C. and Berger, E.A., J. Virol., 67 (1993) 913.
Freed, E.O., Myers, D.J. and Risser, R., J. Virol., 65 (1991) 190.
De Rossi, A., Pasti, M., Mamano, F., Panozzo, M., Dettin, M., Di Bello, C. and Chieco-Bianchi, L., Virology, 184 (1991) 187.
Nehete, P.M., Arlinghaus, R.H. and Sastry, K.J., J. Virol., 67 (1993) 6841.
Mongelli, N., Biasoli, G., Paio, A., Grandi, M. and Ciomei, M. (1991) Eur. Patent no. 91902204.6.
Mongelli, N., Crugnola, A., Lombardi Borgia, A., Ciomei, M., Albanese, C. and Sola, F. (1997) U.K. Patent no. 9713732.
Biasoli, G., Botta, M., Ciomei, M., Corelli, F., Grandi, M., Manetti, F., Mongelli, N. and Paio, A., Med. Chem. Res., 4 (1993) 202.
Manetti, F., Cappello, V., Botta, M., Corelli, F., Mongelli, N., Biasoli, G., Lombardi Borgia, A. and Ciomei, M., Bioorg. Med. Chem., 6 (1998) 947.
Clanton, D.J., Buckheit, R.W., Terpening, S.J., Kiser, R., Mongelli, N., Borgia, A.M., Schultz, R., Narayanan, V., Bader, J.P. and Rice, W.G., Antiviral Res., 27 (1995) 335.
Mohan, P., Wong, M.F., Verma, S., Huang, P.P., Wickramasinghe, A. and Baba, M., J. Med. Chem., 36 (1993) 1996.
Leydet, A., Moullet, C., Roque, J.P., Witvrouw, M., Pannecouque, C., Andrei, G., Snoeck, R., Neyts, J., Schols, D. and De Clercq, E., J. Med. Chem., 41 (1998) 4927.
Lederman, S., Bergmann, J.E., Cleary, A.M., Yellin, M.J., Fusco, P.J. and Chess, L., AIDS Res. Human Retroviruses, 8 (1992) 1599.
Rusconi, S., Moonis, M., Merril, D.P., Pallai, P.V., Neidhardt, E.A., Singh, S.K., Willis, K.J., Osburne, M.S., Profy, A.T., Jenson, J.C. and Hirsch, M.S., Antimicrob. Agents Chemother., 40 (1996) 234.
Patch, R.J., Roberts, J.C., Gao, H., Shi, Z., Gopalsamy, A., Kongsjahju, A., Daniels, K., Kowalczyk, P., van Schravendijk, M.-R., Gordon, K.A. and Pallai, P., Bioorg. Med. Chem. Lett., 24 (1996) 2983.
Cushman, M., Insaf, S., Ruell, J.A., Schaeffer, A. and Rice, W., Bioorg. Med. Chem. Lett., 8 (1998) 833.
Cushman, M., Golebiewski, W.M., McMahan, J.B., Buckheit, R.W., Clanton, D.J., Weislow, O.S., Haugwitz, R.D., Bader, J.P., Graham, L. and Rice, W.G., J. Med. Chem., 37 (1994) 3040.
Program InsightII, distributed by MSI, San Diego, CA.
MacroModel and BatchMin, Version 4.5, Columbia University, New York, NY, 1995.
Mohamadi, F., Richards, N.G.J., Guida, W.C., Liskamp, R., Caufield, C., Chang, G., Hendrickson, T. and Still, W.C., J. Comput.-Aided Mol. Design, 4 (1990) 440.
Guntertofte, K., Liljefors, T., Norrby, P.O. and Pettersson, I., J. Comput. Chem., 17 (1996) 429.
Merz, K.M., Murcko, M.A. and Kollman, P.A., J. Am. Chem. Soc., 113 (1991) 4484.
Leach, A.R. and Kuntz, I.D., J. Comput. Chem., 13 (1992) 730.
Goodford, P.J., J. Med. Chem., 28 (1985) 849.
Boobbyer, D.N.A., Goodford, P.J., McWhinnie, P.M. and Wade, R., J. Med. Chem., 32 (1989) 1083.
Botta, M., Cernia, E., Corelli, F., Manetti, F. and Soro, S., Biochim. Biophys. Acta, 1296 (1996) 121.
Botta, M., Cernia, E., Corelli, F., Manetti, F. and Soro, S., Biochim. Biophys. Acta, 1337 (1997) 302.
Guida, W.C., Bohacek, R.S. and Erion, M.D., J. Comput. Chem., 13 (1992) 214.
Cushman, M., Insaf, S., Paul, G., Ruell, J.A., De Clercq, E., Schols, D., Pannecouque, C., Witvrouw, M., Schaeffer, C.A., Turpin, J.A., Williamson, K. and Rice, W.G., J. Med. Chem., 42 (1999) 1767.
Kwong, P.D., Wyatt, R., Robinson, J., Sweet, R.W., Sodroski, J. and Hendrickson, A., Nature, 393 (1998) 648.
Holloway, M.K., In Kubinyi, H., Folkers, G. and Martin, Y.C. (Eds.), 3D QSAR in Drug Design, Kluwer/Escom, Dordrecht, the Netherlands, 1998, pp. 63-84.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Manetti, F., Corelli, F., Mongelli, N. et al. Research on anti-HIV-1 agents. Investigation on the CD4-Suradista binding mode through docking experiments. J Comput Aided Mol Des 14, 355–368 (2000). https://doi.org/10.1023/A:1008154931914
Issue Date:
DOI: https://doi.org/10.1023/A:1008154931914