Binding of 2-aryl-4-(piperidin-1-yl)butanamines and 1,3,4-trisubstituted pyrrolidines to human CCR5: A molecular modeling-guided mutagenesis study of the binding pocket

Biochemistry

Volumn 42, Issue 6, 2003, Pages 1544-1550

  Castonguay, Laurie A ^a   Weng, Youmin ^a   Adolfsen, William ^a   Di Salvo, Jerry ^a   Kilburn, Ruth ^a   Caldwell, Charles G ^a   Daugherty, Bruce L ^a   Finke, Paul E ^a   Hale, Jeffrey J ^a   Lynch, Christopher L ^a   Mills, Sander G ^a   MacCoss, Malcolm ^a   Springer, Martin S ^a   DeMartino, Julie A ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINES; BINDING ENERGY; BIOLOGICAL MEMBRANES; CRYSTAL STRUCTURE; MOLECULAR STRUCTURE; MUTAGENESIS;

BIOCHEMICAL RECEPTORS;

BIOCHEMISTRY;

ANTIVIRUS AGENT; CHEMOKINE RECEPTOR CCR5; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; PIPERIDINE DERIVATIVE; PYRROLIDINE DERIVATIVE; RECEPTOR BLOCKING AGENT; RHODOPSIN;

ANIMAL CELL; ARTICLE; BINDING SITE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG RECEPTOR BINDING; MOLECULAR MODEL; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION;

ALANINE; AMIDES; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMALS; BINDING SITES; BINDING, COMPETITIVE; BUTANES; CATTLE; CHO CELLS; CRICETINAE; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; PIPERIDINES; PROTEIN STRUCTURE, SECONDARY; PYRROLIDINES; QUATERNARY AMMONIUM COMPOUNDS; RECEPTORS, CCR5; RHODOPSIN; SEQUENCE HOMOLOGY, AMINO ACID; STRUCTURE-ACTIVITY RELATIONSHIP;

ANIMALIA;

EID: 12244267994     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi026639s     Document Type: Article

References (28)

1. Choe, H., Farzan, M., Sun, Y., Sullivan, N., Rollins, B., Ponath, P. D., Wu, L., Mackay, C. R., LaRosa, G., Newman, W., Gerard, N., Gerard, C., and Sodroski, J. (1996) Cell 85, 1135-1148.
2. Doranz, B. J., Rucker, J., Yi, Y., Smyth, R. J., Samson, M., Peiper, S. C., Parmentier, M., Collman, R. G., and Doms, R. W. (1996) Cell 85, 1149-1158.
3. Dragic, T., Litwin, V., Allaway, G. P., Martin, S. R., Huang, Y., Nagashima, K. A., Cayanan, C., Maddon, P. J., Koup, R. A., Moore, J. P., and Paxton, W. A. (1996) Nature 381, 667.
4. Deng, H., Liu, R., Ellmeier, W., Choe, S., Unutmaz, D., Burkhart, M., Di Marzio, P., Marmon, S., Sutton, R. E., Hill, C. M., Davis, C. B., Peiper, S. C., Schall, T. J., Littman, D. R., and Landau, N. R. (1996) Nature 381, 661-666.
5. Alkhatib, G., Combadiere, C., Broder, C. C., Feng, Y., Kennedy, P. E., Murphy, P. M., and Berger, E. A. (1996) Science 272, 1955-1958.
6. Paxton, W. A., Martin, S. R., Tse, D., O'Brien, T. R., Skurnick, J., VanDevanter, N. L., Padian, N., Braun, J. F., Kotler, D. P., Wolinsky, S. M., and Koup, R. A. (1996) Nat. Med. 2, 412-417.
7. Liu, R., Paxton, W. A., Choe, S., Cerandini, D., Martin, S. R., Horuk, R., MacDonald, M. E., Stuhlmann, H., Koup, R. A., and Landau, N. R. (1996) Cell 86, 367-377.
8. Michael, N. L., Chang, G., Louie, L. G., Mascola, J. R., Dondero, D., Birx, D. L., and Sheppard, H. W. (1997) Nat. Med. 3, 338-340.
9. Cocchi, F., DeVico, A. L., Garzino-Demo, A., Arya, S. K., Gallo, R. C., and Lusso, P. (1995) Science 270, 1811-1815.
10. Baba, M., Nishimura, O., Kanzaki, N., Okamoto, M., Sawada, H., Iizawa, Y., Shiraishi, M., Aramaki, Y., Okonogi, K., Ogawa, Y., Mefuro, K., and Fujino, M. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 5698-5703.
11. th Conference of Retroviruses and Opportunistic Infections, San Francisco, CA, Jan 31-Feb 3, Abstract S17.
12. Dorn, C. P., Finke, P. E., Oates, B., Budhu, R. J., Mills, S. G., MacCoss, M., Malkowitz, L., Springer, M. S., Daugherty, B. L., Gould, S. L., DeMartino, J. A., Siciliano, S. J., Carella, A., Carver, G., Holmes, K., Danzeisen, R., Hazuda, D., Kessler, J., Lineberger, J., Miller, M., Schlief, W. A., and Emini, E. A. (2001) Bioorg. Med. Chem. Lett. 11, 259-264.
13. Finke, P. E., Meurer, L. C., Oates, B., Mills, S. G., MacCoss, M., Malkowitz, L., Springer, M. S., Daugherty, B. L., Gould, S. L., DeMartino, J. A., Siciliano, S. J., Carella, A., Carver, G., Holmes, K., Danzeisen, R., Hazuda, D., Kessler, J., Lineberger, J., Miller, M., Schlief, W. A., and Emini, E. A. (2001) Bioorg. Med. Chem. Lett. 11, 265-270.
14. Finke, P. E., Meurer, L. C., Oates, B., Shah, S. K., Loebach, J. L., Mills, S. G., MacCoss, M., Castonguay, L., Malkowitz, L., Springer, M. S., Gould, S. L., and DeMartino, J. A. (2001) Bioorg. Med. Chem. Lett. 11, 2469-2473.
15. Hale, J. J., Budhu, R. J., Holson, E. B., Finke, P. E., Oates, B., Mills, S. G., MacCoss, M., Gould, S. L., DeMartino, J. A., Springer, M. S., Siciliano, S. J., Malkowitz, L. M., Schlief, W. A., Hazuda, D., Miller, M., Kessler, J., Danzeisen, R., Holmes, K., Lineberger, J., Carella, A., Carver, G., and Emini, E. A. (2001) Bioorg. Med. Chem. Lett. 11, 2741-2745.
16. th National Meeting, Washington, DC, Aug 20-25, Abstract MEDI-85.
17. Dragic, T., Trkola, A., Thompson, D. A. D., Cormier, E. G., Kajumo, F. A., Maxwell, E., Lin, S. W., Ying, W., Smith, S. O., Sakmar, T. P., and Moore, J. P. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 5639-5644.
18. Halgren, T. A. (1999) J. Comput. Chem. 20, 720-729.
19. Miller, M. D., Fluder, E. M., Castonguay, L. A., Culberson, J. C., Mosley, R. T., Prendergast, K., Kearsley, S. K., and Sheridan, R. P. (1999) Med. Chem. Res. 9, 513-534.
20. Quanta (2000) Accelrys, Inc., Burlington, MA.
21. Bernstein, F. C., Koetzle, T. F., Williams, G. J. B., Meyer, E. F., and Brice, M. D. (1977) J. Mol. Biol. 112, 535-542.
22. Brooks, B. B., Bruccoleri, R. E., Olafson, B. D., States, D. J., Swaminathan, S., and Karplus, M. (1983) J. Comput. Chem. 4, 187-217.
23. Palczewski, K., Kumasaka, T., Hori, T., Behnke, C. A., Motoshima, H., Fox, B. A., le Trong, I., Teller, D. C., Okada, T., Stenkamp, R. E., Yamamoto, M., and Miyano, M. (2000) Science, 289, 739-745.
24. Samson, M., Labbe, O., Mollereau, C., Vassart, G., and Parmentier, M. (1996) Biochemistry 35, 3362-3367.
25. Daugherty, B. L., and Springer, M. S. (1997) Genomics 41, 294-295.
26. Van Riper, G., Siciliano, S., Fischer, P. A., Meuer, R., Springer, M. S., and Rosen, H. (1993) J. Exp. Med. 177, 851-856.
27. Lynch, C. L., Gentry, A. L., Hale, J. J., Mills, S. G., MacCoss, M., Malkowitz, L., Springer, M. S., Gould, S. L., DeMartino, J. A., Siciliano, S. J., Cascieri, M. A., Doss, G., Carella, A., Carver, G., Holmes, K., Schleif, W. A., Danzeisen, R., Hazuda, D., Kessler, J., Lineberger, J., Miller, M., and Emini, E. A. (2002) Bioorg. Med. Chem. Lett. 12, 677-679.
28. Siciliano, S. J., Kuhmann, S. E., Weng, Y., Madani, N., Springer, M. S., Lineberger, J. E., Danzeisen, R., Miller, M. D., Kavanaugh, M. P., DeMartino, J. A., and Kabat, D. (1999) J. Biol. Chem. 274, 1905-1913.