Abstract
The1H nuclear magnetic resonance (NMR) spectra of angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) and five of its octapeptide analogs as well as angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) and angiotensin III (Arg-Val-Tyr-Ile-His-Pro-Phe) in aqueous solutions (90% H2O/10% D2O) were completely assigned by two-dimensional COSY and ROESY experiments. All of the peptides give rise to two distinct sets of signals. The minor set accounts for about 5% of the total population belowpH 5.5 and increases to 12–20% aroundpH 7.0. The two sets of signals result from acis-trans isomerization of the His-Pro peptide bond with the major resonances arising from thetrans isomer. One analog in which the Pro is replaced with a D-Pro displays a very different isomerization behavior. The measured coupling constants JNH-αCH, the temperature dependence of the amide proton shifts and the relative intensities of the intraresidue and sequential NH-αCH ROEs, are all indicative of an extended backbone conformation for ANGII. However, some evidence for the existence of conformers with local structure involving preferred sidechain positions for the Tyr, His, Phe, and the carboxyl group of the Phe was found, particularly in the ROESY andpH-titration experiments. Moreover,pH effects and the unusual amide exchange behavior of the Arg εNH suggests the presence of interactions between the Asp and Arg sidechains of ANGII. At low temperatures the Arg guanidinium NH2 protons were detected as two broad peaks which are related by sizeable exchange peaks in ROESY experiments. This behavior could be useful as a general probe for the study of Arg sidechain mobility and accessibility in other peptides and proteins
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References
Bax, A., and Davis, D. G. (1985).J. Magn. Reson. 65, 355–366.
Bax, A., Freeman, R., and Morris, G. (1981).J. Magn. Res. 42, 164–168.
Bleich, H. E., Freer, R. J., Stafford, S. S., and Galardy, R. E. (1978).Proc. Natl. Acad. Sci. U.S.A. 75, 3630–3634.
Blundell, T., and Wood, S. (1982).Annu. Rev. Biochem. 51, 123–154.
Boesch, C., Bundi, A., Oppliger, M., and Wüthrich, K. (1978).Eur. J. Biochem. 91, 209–214.
Bothner-By, A. A., Stephens, R. L., Lee, J., Warren, C. D., and Jeanloz, R. W. (1984).J. Amer. Chem. Soc. 106, 811–813.
Bundi, A., Andreatta, R. H., and Wüthrich, K. (1978).Eur. J. Biochem. 91, 201–208.
Carver, J. A. (1987).Eur. J. Biochem. 168, 193–199.
Clore, G. M., and Gronenborn, A. M. (1987).Prot. Eng. 1, 275–288.
Deslauriers, R., Ralston, E., and Somorjai, R. L. (1977).J. Mol. Biol. 113, 697–710.
Duncia, J. V., Chiu, A. T., Carini, D. J., Gregory, G. B., Johnson, A. L., Price, W. A., Wells, G. J., Wong, P. C., Calabrese, J. C., and Timmermans, P. (1990).J. Med. Chem. 33, 1312–1329.
Dyson, H. J., Rance, M., Houghten, R. A., Lerner, R. A., and Wright, P. E. (1988).J. Mol. Biol. 201, 161–201.
Ernst, R. R., Bodenhausen, G., and Wokaun, A. (1987).Principles of Nuclear Magnetic Resonance in One and Two Dimensions, Clarendon Press, Oxford.
Fermandjian, S., Fromageot, P., Tistchenko, A. M., Leiknam, J. P., and Lutz, M. (1972).Eur. J. Biochem. 28, 174–182.
Goghari, M. H., Franklin, K. J., and Moore, G. J. (1986).J. Med. Chem. 29, 1121–1124.
Griesinger, C., and Ernst, R. R. (1987).J. Magn. Reson. 75, 261–271.
Kaptein, R., Boelens, R., Scheek, R. M., and van Gunsteren, W. F. (1988).Biochemistry 27, 5389–5395.
Kessler, H. (1982).Angew. Chem. Int. Ed. Engl. 21, 512–523.
Kördel, J., Forsén, S., Drakenberg, T., and Chazin, W. (1990).Biochemistry 29, 4400–4409.
Lenkinski, R. E., Stephens, R. L., and Krishna, N. R. (1981).Biochemistry 20, 3122–3126.
Maia, H. L., Orrell, K. G., and Rydon, H. N. (1971).Chem. Comm. 1209–1210.
Malikayil, J. A., Lerch, K., and Armitage, I. M. (1988).Biochemistry 28, 2991–2995.
Marion, D., and Wüthrich, K. (1983).Biochem. Biophys. Res. Commun. 113, 967–974.
Matsoukas, J. M., Bigam, G., Zhou, N., and Moore, G. J. (1990).Peptides 11, 359–366.
Montelioni, G. T., Arnold, E., Meinwald, Y. C., Stinston, E. R., Denton, J. B., Huang, S.-G., Clardy, J., and Scheraga, H. A. (1984).J. Am. Chem. Soc. 160, 7946–7958.
Moore, G. J., and Matsoukas, J. M. (1985).Biosci. Rep. 5, 407–416.
Motta, A., Picone, D., Tancredi, T., and Temussi, P. A. (1987).J. Magn. Reson. 75, 364–370.
Ni, F., Scheraga, H. A., and Lord, S. T. (1988).Biochemistry 27, 4481–4491.
Ondetti, M. A., and Cushman, D. W. (1982).Annu. Rev. Biochem. 51, 283–308.
Otter, A., Scott, P. G., and Kotovych, G. (1988).Biochemistry 27, 3560–3567.
Paiva, T. B., Paiva, A. C. M., and Scheraga, H. A. (1963).Biochemistry 2, 1327–1334.
Pardi, A., Billeter, M., and Wüthrich, K. (1984).J. Mol. Biol. 180, 741–751.
Plateau, P., and Gueron, M. (1982).J. Am. Chem. Soc. 104, 7310–7311.
Prinz, M. P., Nemethy, G., and Bleich, H. (1972).Nature (London), New Biol. 237, 135–140.
Rance, M., Sørenson, O. W., Bodenhausen, G., Wagner, G., Ernst, R. R., and Wüthrich, K. (1983).Biochem. Biophys. Res. Commun. 131, 1094–1102.
Smeby, R. R., Arakawa, K., Bumpus, F. M., and Marsh, M. M. (1962).Biochim. Biophys. Acta 58, 550–557.
Turker, R. K., Hall, M. N., Yamamoto, M., Sweet, C. S., and Bumpus, F. M. (1972).Science 177, 1203–1205.
Weinkam, R. J., and Jorgensen, E. C. (1971).J. Am. Chem. Soc. 93, 7038–7044.
Williamson, M. P., Hall, M. J., and Handa, B. K. (1986).Eur. J. Biochem. 158, 527–536.
Wright, P. E., Dyson, H. J., and Lerner, R. A. (1988).Biochemistry 27, 7167–7175.
Wüthrich, K. (1986).NMR of Proteins and Nucleic Acids, John Wiley & Sons, New York.
Wüthrich, K. (1989).Science 243, 45–50.
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Zhou, N., Moore, G.J. & Vogel, H.J. Proton NMR studies of angiotensin II and its analogs in aqueous solution. J Protein Chem 10, 333–343 (1991). https://doi.org/10.1007/BF01025632
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DOI: https://doi.org/10.1007/BF01025632