Skip to main content
SpringerLink
Log in

Prediction of location of active sites in biologically active peptides

  • Published:
Journal of Protein Chemistry Aims and scope Submit manuscript

Abstract

In a previous paper we demonstrated that the short-range compact regions in atrial natriuretic factor (α-hANF) predicted by the average distance map (ADM) correspond to its active sites [Kikuchi,J. Protein Chem.11, 579–581 (1992)]. In the present paper we apply the same method to other bioactive peptides and peptidic enzyme inhibitors. We again observe that active sites in each peptide are contained in short-range compact regions predicted by the ADM for the peptide. This demonstrates that the ADM method predicts the possible location of active sites in biologically active peptides in general. The possibility of practical application of the present method to rational drug design is also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anderson, N. H., Chen, C., Marschner, T. M., Krystek, S. R., Jr., and Bassolino, D. (1992).Biochemistry 31, 1280–1295.

    Article  Google Scholar 

  • Bode, W., Papamokos, E., Musil, D., Seemuller, U., and Fritz, H. (1986).EMBO J. 5, 813–818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bortmann, P., Hoflack, J., Pelton, J., and Saudek, V. (1991).Neurochem. Int. 18, 491–496.

    Article  CAS  PubMed  Google Scholar 

  • Chan, J. Y., Ngai, P. K., Rink, H., Dennis, S., and Schlaeppi, J.-M. (1990).FEBS Lett. 261, 287–290.

    Article  Google Scholar 

  • Dennis, S., Wallace, A., Hofsteenge, J., and Stone, S. R. (1990).Eur. J. Biochem. 188, 61–66.

    Article  CAS  PubMed  Google Scholar 

  • Dodt, J., Köhler, S., Scmitz, T., and Wilhelin, B. (1990).J. Biol. Chem. 265, 713–718.

    Article  CAS  PubMed  Google Scholar 

  • Endo, S., Inooka, H., Ishibashi, Y., Kitada, C., Mizuta, E., and Fujino, M. (1989).FEBS Lett. 257, 149–154.

    Article  CAS  PubMed  Google Scholar 

  • Filep, J. G., Rousseau, A., Fournier, A., and Sirois, P. (1992).Eur. J. Pharmacol. 220, 263–266.

    Article  CAS  PubMed  Google Scholar 

  • Grütter, M. G., Priestle, J. P., Rahuel, J., Grossenbacher, H., Bode, W., Hofsteenge, J., and Stone, S. R. (1990).EMBO J. 9, 2361–2365.

    Article  PubMed  PubMed Central  Google Scholar 

  • Habener, J. F., Rosenblatt, M., and Potts, J. T., Jr. (1984).Physiol. Rev. 64, 985–1053.

    Article  CAS  PubMed  Google Scholar 

  • Janes, R. W., Peapus, D. H., and Wallace, B. A. (1994).Nature Struct. Biol. 1, 311–319.

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi, T. (1992).J. Protein Chem. 11, 579–581.

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi, T., Némethy, G., and Scheraga, H. A. (1988a).J. Protein Chem. 7, 427–471.

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi, T., Némethy, G., and Scheraga, H. A. (1988b).J. Protein Chem. 7, 491–507.

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi, T., Okamoto, M., Griser, M., Schmitz, A., Gohda, K., Takai, M., and Fujita, N. (n.d.). To be published.

  • Kimura, S., Kasuya, Y., Sawamura, T., Shinmi, O., Sugita, Y., Yanagisawa, M., Goto, K., and Masaki, T. (1988).Biochem. Biophys. Res. Commun. 156, 1182–1186.

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi, Y., Ohkubo, T., Kyogoku, Y., Koyama, S., Kobayashi, M., and Go, N. (1988).J. Biochem. 104, 322–325.

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi, Y., Sato, A., Takashima, H., Tamaoki, H., Nishimura, S., Kyogoku, Y., Ikenaka, K., Kondo, T., Mikoshiba, K., Hojo, H., Aimoto, S., and Moroder, L. (1991).Neurochem. Int. 18, 525–534.

    Article  CAS  PubMed  Google Scholar 

  • Konishi, Y., Frazier, R. B., Olins, G. M., Blehm, D. J., Tjoeng, F. S., Zupec, M. E., and Whipple, D. E. (1987). InPeptides, Chemistry and Biology (Marshall, G. R., ed.), Escom, Leiden, pp. 479–481.

    Google Scholar 

  • Koyama, S., Kobayashi, Y., Ohkubo, T., Kyogoku, Y., Sato, A., Kobayashi, M., and Go, N. (1990).Protein Eng. 3, 393–402.

    Article  CAS  PubMed  Google Scholar 

  • Krstenansky, J. L., and Mao, S. J. T. (1987).FEBS Lett. 211, 10–16.

    Article  CAS  PubMed  Google Scholar 

  • Ladner, R. C. (1995).Trends Biotech. 13, 426–430.

    Article  CAS  Google Scholar 

  • Mao, S. J. T., Yates, M. T., Owen, T., Owen, J., and Krstenansky, J. L. (1988).Biochemistry 27, 8170–8173.

    Article  CAS  PubMed  Google Scholar 

  • McPhalen, C. A., Schnebli, H. P., and James, M. N. G. (1985).FEBS Lett. 188, 55–58.

    Article  CAS  PubMed  Google Scholar 

  • Mills, R. G., O'Donoghue, S. I., Smith, R., and King, G. F. (1992).Biochemistry 31, 5640–5645.

    Article  CAS  PubMed  Google Scholar 

  • Munro, S., Craik, D., McConville, C., Hall, J., Searle, M., Bicknell, W., Scanlon, D., and Chandler, C. (1991).FEBS Lett. 278, 9–13.

    Article  CAS  PubMed  Google Scholar 

  • Nakajima, K., Kubo, S., Kumagaye, S.-I., Nishio, H., Tsunemi, M., Inui, T., Kuroda, H., Chino, N., Watanabe, T. X., Kimura, T., and Sakakibara, S. (1989).Biochem. Biophys. Res. Commun. 163, 424–429.

    Article  CAS  PubMed  Google Scholar 

  • Ni, F., and Konishi, Y. (1990).Biochemistry 29, 4479–4489.

    Article  CAS  PubMed  Google Scholar 

  • Panek, R. L., Major, T. C., Taylor, D. G., Hingorani, G. P., Dunbar, J. B., Doherty, A. M., and Rapundalo, S. T. (1992).Biochem. Biophys. Res. Commun. 183, 572–576.

    Article  CAS  PubMed  Google Scholar 

  • Potts, J. T. Jr., Kronenberg, H. M., and Rosenblatt, M. (1982).Adv. Protein Chem. 35, 323–396.

    Article  CAS  PubMed  Google Scholar 

  • Reily, M. D., and Dunbar, J. B. Jr., (1991).Biochem. Biophys. Res. Commun. 178, 570–577.

    Article  CAS  PubMed  Google Scholar 

  • Rizo, J., and Gierasch, L. M. (1992).Annu. Rev. Biochem. 61, 387–418.

    Article  CAS  PubMed  Google Scholar 

  • Rosenblatt, M. G., Segre, G. V., Tyler, G. A., Shepard, G. L., Nussbaum, S. R., and Potts, J. T., Jr. (1980).Endocrinology 106, 545–550.

    Article  Google Scholar 

  • Rovero, P., Patacchini, R., and Maggi, C. A. (1990).Br. J. Pharmacol. 101, 232–234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rydel, T. J., Ravichandran, K. G., Tulinsky, A., Bode, W., Huber, R., Roitsch, C., and Fenton II, J. W. (1990).Science 249, 277–280.

    Article  CAS  PubMed  Google Scholar 

  • Saudek, V., Hoflack, J., and Pelton, J. T. (1991).Int. J. Peptide Protein Res. 37, 174–179.

    Article  CAS  Google Scholar 

  • Seemueller, W., Meier, M., Ohlsson, K. Mueller, H.-P., and Fritz, H. (1977).Hoppe-Seyler's Z. Physiol. Chem. 358, 1105–1117.

    Article  CAS  Google Scholar 

  • Siligardi, G., and Drake, A. F. (1995).Biopolymers (Protein Sci.) 37, 281–292.

    Article  CAS  Google Scholar 

  • Strickland, L. A., Bozzato, R. P., and Krois, K. A. (1993).Biochemistry 32, 6050–6057.

    Article  CAS  PubMed  Google Scholar 

  • Tamaoki, H., Kobayashi, Y., Nishimura, S., Ohkubo, T., Kyogoku, Y., Nakajima, K., Kumagaye, S.-I., Kimura, T., and Sakakibara, S. (1991).4, 509–518.

  • Yue, S.-Y., DiMaio, J., Szewczuk, Z., Purisima, E. O., Ni, F., and Konishi, Y. (1992).Protein Eng. 5, 77–85.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. International Research Laboratories, Ciba-Geigy (Japan) Limited, 10-66 Miyuki-cho, 665, Takarazuka, Japan

    Takeshi Kikuchi

Authors
  1. Takeshi Kikuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kikuchi, T. Prediction of location of active sites in biologically active peptides. J Protein Chem 15, 539–545 (1996). https://doi.org/10.1007/BF01908535

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01908535

Key words

Search

Navigation