Summary
The internal mobility of three isomeric cyclic RGD hexapeptides designed to contain two β-turns in defined positions, cyclo(Arg-Gly-Asp-Gly-d-Pro-Pro) (I), cyclo(Arg-Gly-Asp-d-Pro-Gly-Pro) (II) and cyclo(Arg-Gly-Asp-d-Pro-Pro-Gly) (III), have been studied by 13C NMR longitudinal and transverse relaxation experiments and measurements of steady-state heteronuclear {1H}-13C NOE enhancement with 13C at natural abundance. The data were interpreted according to the model-free formalism of Lipari and Szabo, which is usually applied to data from macromolecules or larger sized peptides with overall rotational correlation times exceeding 1 ns, to yield information about internal motions on the 10–100 ps time scale. The applicability of the model-free analysis with acceptable uncertainties to these small peptides, with overall rotational correlation times slightly below 0.3 ns, was demonstrated for this specific instance. Chemical exchange contributions to T2 from slower motions were also identified in the process. According to the order parameters obtained for its backbone α-carbon atoms, II has the most rigid backbone conformation on the 10–100 ps time scale, and I the most flexible. This result coincides with the results of earlier NMR-constrained conformational searches, which indicated greatest uncertainty in the structure of I and least in II.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abragam, A. (1961) Principles of Nuclear Magnetism, Clarendon Press Oxford, pp. 264–353.
Ali, F.E. and Samanen, J.M. (1992) In Innovations and Perspectives in Solid Phase Synthesis: Peptides, Polypeptides and Oligonucleotides (Ed., Epton, R.), Intercept Ltd., Hanover, U.K., pp. 333–335.
Barbato, G., Ikura, M., Kay, L.E., Pastor, R.W. and Bax, A. (1992) Biochemistry, 31, 5269–5278.
Bean, J.W., Kopple, K.D. and Peishoff, C.E. (1992) J. Am. Chem. Soc., 114, 5328–5334.
Bevington, P.R. (1969) Data Reduction and Error Analysis for the Physical Sciences, McGraw-Hill Inc., New York, NY.
Blackledge, M.J., Brüschweiler, R., Griesinger, C., Schmidt, J.M., Xu, P. and Ernst, R.R. (1993) Biochemistry, 32, 10960–10974.
Bloom, M., Reeves, L.W. and Wells, E.J. (1965) J. Chem. Phys., 42, 1615–1624.
Bonvin, A.M.J.J., Boelens, R. and Kaptein, R. (1993) In Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications, Vol. 2 (Eds, VanGunsteren, W.F., Weiner, P.K. and Wilkinson, A.J.), ESCOM, Leiden, pp. 407–440.
Bremi, T., Ernst, M. and Ernst, R.R. (1994) J. Phys. Chem., 98, 9322–9334.
Carr, H.Y. and Purcell, E.M. (1954) Phys. Rev., 94, 630–638.
Chen, Y., Suri, A.K., Kominos, D., Sanyal, G., Naylor, A.M., Pitzenberger, S.M., Garsky, V.M., Levy, R.M. and Baum, J. (1994) J. Biomol. NMR, 4, 307–324.
Clore, G.M., Driscoll, P.C., Wingfield, P.T. and Gronenborn, A.M. (1990a) Biochemistry, 29, 7387–7401.
Clore, G.M., Szabo, A., Bax, A., Kay, L.E., Driscoll, P.C. and Gronenborn, A.M. (1990b) J. Am. Chem. Soc., 112, 4989–4991.
Dellwo, M.J. and Wand, A.J. (1989). J. Am. Chem. Soc., 111, 4571–4578.
Deverell, C., Morgan, R.E. and Strange, J.H. (1970) Mol. Phys., 18, 553–559.
Fushman, D., Weisemann, R., Thüring, H. and Rüterjans, H. (1994) J. Biomol. NMR, 4, 61–78.
Gutowsky, H.S., McCall, D.M. and Slichter, C.P. (1953) J. Chem. Phys., 21, 279–292.
Jarvis, J.A. and Craik, D.J. (1995) J. Magn. Reson. Ser. B, 107, 95–106.
Kay, L.E., Torchia, D.A. and Bax, A. (1989) Biochemistry, 28, 8972–8979.
Kay, L.E., Nicholson, L.K., Delaglio, F., Bax, A. and Torchia, D.A. (1992) J. Magn. Reson., 97, 359–375.
King, R. and Jardetzky, O. (1978) Chem. Phys. Lett., 55, 15–18.
Kopple, K.D., Go, A., Logan, R.H. and Savrda, J. (1972) J. Am. Chem. Soc., 94, 973–981.
Kopple, K.D., Wang, Y.-S., Cheng, A.G. and Bhandary, K.K. (1988) J. Am. Chem. Soc., 110, 4169–4176.
Lipari, G. and Szabo, A. (1980) Biophys. J., 30, 489–506.
Lipari, G. and Szabo, A. (1982) J. Am. Chem. Soc., 104, 4545–4570.
Meiboom, S. and Gill, D. (1958) Rev. Sci. Instrum., 29, 688–691.
Neuhaus, D. and Williamson, M.P. (1989) The Nuclear Overhauser Effect in Structural and Conformational Analysis, VCH Publishers Inc., New York, NY, pp. 23–61.
Palmer III, A.G., Rance, M. and Wright, P.E. (1991) J. Am. Chem. Soc., 113, 4371–4380.
Palmer III, A.G., Skelton, N.J., Chazin, W.J., Wright, P.E. and Rance, M. (1992) Mol. Phys., 75, 699–711.
Palmer III, A.G., Hochstrasser, R.A., Millar, D.P., Rance, M. and Wright, P.E. (1993) J. Am. Chem. Soc., 115, 6333–6345.
Peishoff, C.E., Ali, F.E., Bean, J.W., Calvo, R., D'Ambrosio, C.A., Eggleston, D.S., Hwang, S.M., Kline, T.P., Koster, P.F., Nichols, A., Powers, D., Romoff, T., Samanen, J.M., Stadel, J., Vasko, J.A. and Kopple, K.D. (1992) J. Med. Chem., 35, 3962–3969.
Peng, J.W., Thanabal, V. and Wagner, G.J. (1991) J. Magn. Reson., 95, 421–427.
Peng, J.W. and Wagner, G. (1992a) Biochemistry, 31, 8571–8586.
Peng, J.W. and Wagner, G. (1992b) J. Magn. Reson., 98, 308–332.
Press, W.H., Flannery, B.P., Teukolsky, S.A. and Vetterling, W.T. (1986) Numerical Recipes, Cambridge University Press, Cambridge, pp. 498–546.
Richarz, R., Nagayama, K. and Wüthrich, K. (1980) Biochemistry, 19, 5189–5196.
Schneider, D.M., Dellwo, M.J. and Wand, A.J. (1992) Biochemistry, 31, 3645–3652.
Shaka, A.J., Keeler, J., Frenkiel, T. and Freeman, R. (1983) J. Magn. Reson., 53, 335–338.
Silverstein, R.M., Bassler, G.C. and Morrill, T.C. (1981) Spectrometric Identification of Organic Compounds, 4th ed., Wiley, New York, NY, pp. 249–281.
Stone, M.J., Fairbrother, W.J., Palmer, A.G., Reizer, J., Saier, M.H. and Wright, P.E. (1992) Biochemistry, 31, 4394–4406.
Vold, R.L., Waugh, J.S., Klein, M.P. and Phelps, D.E. (1968) J. Chem. Phys., 48, 3831–3832.
Williams, R.J.P. (1989) Eur. J. Biochem., 183, 479–497.
Zieger, G. and Sterk, H. (1992) Magn. Reson. Chem., 30, 387–392.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Briand, J., Kopple, K.D. Internal mobility of cyclic RGD hexapeptides studied by 13C NMR relaxation and the model-free approach. J Biomol NMR 6, 347–360 (1995). https://doi.org/10.1007/BF00197634
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00197634