The three-dim-nsional structure of a peptide deduced from conformational analyses (nuclear magnetic resonance and circular dichroism spectroscopies) and/or from energy calculations should provide an insight into the structural requirements of the binding protein, if this structure has any relevance to the conformation which interacts with the binding protein. A decisive contribution to overcome this problem has been the design of constrained analogues of the peptide which simulate the predicted conformers. Indeed such rigidified analogues, if active, must contribute to a more accurate description of the bioactive conformation[l]. We have established, using NMR and CD spectroscopies, that the three-dimensional structure of SP is strongly influenced by its environment. The main features of the conformation model we have proposed are the flexibility of the N-terminal Arg-ProLys, the a-helical folding of the core of SP, Pro-Gln-Gln-Phe-Phe, and the folding of the C-terminal carboxamide towards the primary amides of Gin5 and Gln6 [2] The validity of this model has been checked by the means of constrained cyclic analogues of SP. Therefore, we have synthesized two groups of disulfide bridged analogues of SP.
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Ploux, O. et al. (1987). Conformationally Restricted Analogues of Substance P. In: Henry, J.L., Couture, R., Cuello, A.C., Pelletier, G., Quirion, R., Regoli, D. (eds) Substance P and Neurokinins. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-4672-5_21
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