Abstract
Early reports that acyclic analogues of oxytocin and vasopressin (AVP) have drastically reduced agonistic activities established as dogma that an intact hexapeptide ring structure is essential for the pharmacological activities of analogues of neurohypophysial hormones1. Thus, virtually all the many hundreds of agonistic and antagonistic analogues of the neurohypophysial peptides that have been reported contain an intact ring1–3. Here we report that an intact ring is not essential for binding of antagonistic AVP analogues to vasopressor (V1) or antidiuretic (V2) AVP receptors. In fact, one acyclic AVP analogue seems to be about as potent as any previously reported cyclic V2 antagonist. This finding suggests new possibilities for the design of AVP analogues as pharmacological probes and for therapeutic use. Similar modifications might be useful in the design of analogues of other cyclic peptides, such as calcitonin, somatostatin and the atrial natriuretic factors.
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References
Berde, B. & Boissonnas, R. A. in Handbook of Experimental Pharmacology Vol. 23 (ed. Berde, B.) 802–807 (Springer, Berlin, 1968).
Hruby, V. J. & Smith, C. W. in The Peptides Vol. 8 (eds Udenfriend, S. & Meienhofer, J.) 77–207 (Academic, Orlando, Florida, 1987).
Manning, M., Bankowski, K. & Sawyer, W. H. in Vasopressin, Principles and Properties (eds Gash, D. M. & Boer, G. J.) 335–368 (Plenum, New York, 1987).
Manning, M. et al. J. med. Chem. 25, 45–50 (1982).
Merrifield, R. B. J. Am. chem. Soc. 85, 2149–2154 (1963).
Merrifield, R. B. Science 232, 341–347 (1986).
Sawyer, W. H. Endocrinology 63, 694–698 (1958).
Sawyer, W. H. et al. Science 212, 49–51 (1981).
Dekanski, J. Br. J. Pharmac. 7, 567–572 (1952).
Dyckes, D. F., Nestor, J. J. Jr, Ferger, M. F. & du Vigneand, V. J. med. Chem. 17, 250–252 (1974).
Manning, M. & Sawyer, W. H. J. cardiovasc. Pharmac. Suppl. 8, 529–535 (1986).
Ali, F. E. et al. J. med. Chem. 29, 984–988 (1986).
Nelson, C. F. et al. J. med. Chem. 29, 2425–2426 (1986).
De Wied, D., Gaffori, O., van Ree, J. M. & de Jong, W. Nature 308, 276–278 (1984).
Johnston, C. I. J. Hypertension 3, 557–569 (1985).
Schrier, R. W. New Engl. J. Med. 312, 1121–1123 (1985).
Orlowski, R. C., Epand, R. M. & Stafford, A. R. Eur. J. Biochem. 163, 399–402 (1987).
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Manning, M., Przybylski, J., Olma, A. et al. No requirement of cyclic conformation of antagonists in binding to vasopressin receptors. Nature 329, 839–840 (1987). https://doi.org/10.1038/329839a0
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DOI: https://doi.org/10.1038/329839a0
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