Duplaa H, Chassaing G, Lavielle S, Beaujouan J C, Torrens Y, Saffroy M, Glowinski J, D'Orléans Juste P, Regoli D, Carruette A
Laboratoire de Chimie Organique Biologique, CNRS URA 493, Université Paris VI, France.
Neuropeptides. 1991 Aug;19(4):251-7. doi: 10.1016/0143-4179(91)90092-w.
The D-enantiomer of residues 2, 4, 5, 6, 7, 8, 10 and 11 was introduced in the sequence of Substance P: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2. The achiral glycine residue was replaced by a D-Ala residue. Regarding NK-1 binding potencies or activities, changing to the D-enantiomer in positions 2, 4 or 5 did not modify the pharmacological patterns of the resulting peptides. Introduction of a D-residue in the 6 to 11 sequence drastically decreased the potency of the D-analogues with the exception of [D-Leu10]SP which was found only three times less potent than SP in contracting the guinea-pig ileum. No clear cut evidence between the binding potencies and activities on NK-1, NK-2 and NK-3 assays, was observed which allows a more rational design of tachykinins antagonists.
将P物质（Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2）序列中第2、4、5、6、7、8、10和11位残基的D-对映体引入其中。非手性甘氨酸残基被D-丙氨酸残基取代。关于NK-1结合亲和力或活性，在第2、4或5位变为D-对映体不会改变所得肽的药理模式。在6至11位序列中引入D-残基会显著降低D-类似物的亲和力，只有[D-Leu10]SP例外，在收缩豚鼠回肠方面其效力仅比P物质低三倍。在NK-1、NK-2和NK-3试验的结合亲和力和活性之间未观察到明确的证据，这使得速激肽拮抗剂的设计更加合理。
