Conformation of the metastasis-inhibiting laminin pentapeptide

Journal of Protein Chemistry - Tập 8 - Trang 149-157 - 1989
Paul W. Brandt-Rauf1, Matthew R. Pincus2, Robert P. Carty3, Jack Lubowsky4, Matthew Avitable4, John Carucci5, Randall B. Murphy5
1Division of Environmental Sciences and Department of Medicine, Columbia-Presbyterian Medical Center, New York
2Department of Pathology, SUNY Health Science Center, Syracuse
3Department of Biochemistry, SUNY Downstate Medical Center, Brooklyn
4Scientific Academic Computing Center, SUNY Downstate Medical Center, Brooklyn
5Department of Chemistry, New York University, New York

Tóm tắt

The binding of cancer cells to the basement membrane glycoprotein laminin appears to be a critical step in the metastatic process. This binding can be inhibited competitively by a specific pentapeptide sequence (Tyr-Ile-Gly-Ser-Arg) of the laminin B1 chain, and this peptide can prevent metastasis formationin vivo. However, other similar pentapeptide sequences (e.g., Tyr-Ile-Gly-Ser-Glu) have been found to be much less active in metastasis inhibition, raising the possibility that such amino acid substitutions produce structural changes responsible for altering binding to the laminin receptor. In this study, conformational energy analysis has been used to determine the three-dimensional structures of these peptides. The results indicate that the substitution of Glu for the terminal Arg produces a significant conformational change in the peptide backbone at the middle Gly residue. These results have important implications for the design of drugs that may be useful in preventing metastasis formation and tumor spread.

Tài liệu tham khảo

Barlow, D. P., Green, N. M., Kurkinen, M., and Hogan, B. L. M. (1984).EMBO J. 3, 2355–2362. Barsky, S. H., Rao, C. N., Williams, J. E., and Liotta, L. A. (1984).J. Clin. Invest. 74, 843–848. Brandt-Rauf, P. W., Carty, R. P., Chen, J., Avitable, M., Lubowsky, J., and Pincus, M. R. (1988).Proc. Natl. Acad. Sci. USA in press. Brandt-Rauf, P. W., Pincus, M. R., Carty, R. P., Lubowsky, J., and Avitable, M. (1985).J. Protein Chem. 4, 353–362. Brandt-Rauf, P. W., Pincus, M. R., Maizel, J., Carty, R. P., Lubowsky, J., Avitable, M., Shipley, J., and Wagner, R. R. (1987).J. Protein Chem. 6, 463–472. Dygert, M., Go, N., and Scheraga, H. A. (1975).Macromolecules 8, 750–761. Graf, J., Iwamoto, Y., Sasaki, M., Martin, G. R., Kleinman, H. K., Robey, F. A., and Yamada, Y. (1987).Cell 48, 989–996. Horan-Hand, P., Thor, A., Schlom, J., Rao, C. N., and Liotta, L. (1985).Cancer Res. 45, 2713–2719. Howe, C. C., and Dietzschold, B. (1983).Dev. Biol. 98, 385–391. Iwamoto, Y., Robey, F. A., Graf, J., Sasaki, M., Kleinman, H. K., Yamada, Y., and Martin, G. R. (1987).Science 238, 1132–1134. Miller, M. H., and Scheraga, H. A. (1976).J. Polymer Sci. Polymer Symp. 54, 171–200. Paulsson, M., Deutzmann, R., Timpl, R., Dalzoppo, D., Odermatt, E., and Engel, J. (1985).EMBO J. 4, 309–316. Pincus, M. R., and Brandt-Rauf, P. W. (1985).Proc. Natl. Acad. Sci. USA 82, 3596–3600. Pincus, M. R., and Brandt-Rauf, P. W. (1986).Cancer Invest. 4, 185–195. Pincus, M. R., and Klausner, R. D. (1982).Proc. Natl. Acad. Sci. USA 79, 3413–3417. Pincus, M. R., Klausner, R. D., and Scheraga, H. A. (1982).Proc. Natl. Acad. Sci. USA 79, 5107–5110. Pincus, M. R., Gerewitz, F., Schwartz, R. H., and Scheraga, H. A. (1983a).Proc. Natl. Acad. Sci. USA 80, 3297–3300. Pincus, M. R., van Renswoude, J., Harford, J. B., Chang, E. H., Carty, R. P., and Klausner, R. D. (1983b).Proc. Natl. Acad. Sci. USA 80, 5253–5257. Pincus, M. R., Brandt-Rauf, P. W., Carty, R. P., Lubowsky, J., and Avitable, M. (1985).J. Protein Chem. 4, 345–352. Pincus, M. R., Carty, R. P., Chen, J., Lubowsky, J., Avitable, M., Shah, D., Scheraga, H. A., and Murphy, R. B. (1987a).Proc. Natl. Acad. Sci. USA 84, 4821–4825. Pincus, M. R., Brandt-Rauf, P. W., Carty, R. P., Lubowsky, J., Avitable, M., Gibson, K. D., and Scheraga, H. A. (1987b).Proc. Natl. Acad. Sci. USA 84, 8375–8379. Sasaki, M., Kato, S., Kohno, K., Martin, G. R., and Yamada, Y. (1987).Proc. Natl. Acad. Sci. USA 84, 935–939. Scheraga, H. A. (1984).Carlsberg Res. Commun. 49, 1–55. Simon, I., Nemethy, G., and Scheraga, H. A. (1980).Macromolecules 11, 797–804. Terranova, V. P., Liotta, L. A., Russo, R. G., and Martin, G. R. (1982).Cancer Res. 42, 2265–2269. Terranova, V. P., Rao, C. N., Kalebic, T., Margulies, I. M., and Liotta, L. A. (1983).Proc. Natl. Acad. Sci. USA 80, 444–448. Terranova, V. P., Williams, J. E., Liotta, L. A., and Martin, G. R. (1984).Science 226, 982–985. Turpeenniemi-Hujanen, T., Thorgeirsson, V. P., Rao, C. N., and Liotta, L. A. (1986).J. Biol. Chem. 261, 1883–1889. Zimmerman, S. S., Pottle, M. S., Nemethy, G., and Scheraga, H. A. (1977).Macromolecules 10, 1–9.
Thông tin
Thông tin xuất bản

Journal of Protein Chemistry

Tập 8

149-157

Thông tin tác giả