Abstract
In an effort to determine the role of the acidic group in the receptor binding of N-(2-hydroxy-4-nitrophenyl)-N′-(phenyl) urea, an interleukin-8B receptor antagonist, its binding and that of several analogs was measured as a function of pH. These titrations indicate that these ureas bind most strongly in their anionic form. Studies of antagonists, with different acidities, demonstrated that the greatest change in binding of each urea occurred around the pKa of the compound being examined. The studies suggest that the increase in binding of the antagonists at higher pH is a result of the increased negative charge on the compounds rather than the effects of pH on the receptor or radioligand.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Holmes, W.E., Lee, J., Kuang, W.J., Rice, G.C. and Wood, W.I., Science, 253 (1991) 1278.
Murphy, P.M. and Tiffany, H.L., Science, 253 (1991) 1280.
Beckmann, M.P., Munger, W.E., Kozlosky, C., VandenBos, T., Price, V., Lyman, S., Gerard, N.P., Gerard, C. and Cerretti, D.P., Biochem. Biophys. Res. Commun., 179 (1991) 784.
Thompson, S.K., Veber, D.F., Jurewicz, A.J., Peishoff, C.E., Lee, J.A. and White, J.R., Int. J. Pept. Protein Res., 47 (1996) 214.
Freidinger, R., In Junkel, E. (Ed.) Progress in Drug Research, Vol. 40, Birkhäuser, Basel, 1993, pp. 33–98.
Kraft, A. and Anderson, W., Nature, 301 (1983) 621.
Cerami, A. and Manning, J.M., Proc. Natl. Acad. Sci. USA, 68 (1971) 1180.
Widdowson, K.L., Veber, D.F., Nie, H., Jurewicz, A.J., Foley, J.J., Sarau, H.M., Lee, J. and White, J.R., In Ramage, R. (Ed.) Peptides 1996, Proceedings of the 24th European Peptide Symposium, Mayflower Publishing (accepted).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Widdowson, K., Nie, H., Jurewicz, A.J. et al. The role of the anionic groups in the receptor binding of interleukin-8 antagonists. Letters in Peptide Science 5, 235–239 (1998). https://doi.org/10.1023/A:1008870816677
Issue Date:
DOI: https://doi.org/10.1023/A:1008870816677