Ciajolo M R, Balboni G, Picone D, Salvadori S, Tancredi T, Temussi P A, Tuzi A
Department of Chemistry, University of Naples Federico II, Italy.
Int J Pept Protein Res. 1995 Aug;46(2):134-8. doi: 10.1111/j.1399-3011.1995.tb01328.x.
delta-Selective antagonism of [L-Tic2]-peptides, including the simple dipeptide Tyr-L-Tic-NH2, is linked to the Tyr-Tic-"recognition site". In order to gain further information on the conformational preferences of the Tyr-Tic-moiety we have undertaken a structural study of a cyclic analog, the diketopiperazine of Tyr-Tic. A conformational study of cyclo[-Tyr-Tic-], that is almost devoid of opioid activity, can also be useful to discriminate between the role of the two aromatic rings and of the basic nitrogen in determining antagonism. The structure of cyclo[-Tyr-Tic-] has been solved in a DMSO/water solution at 278 K by NMR spectroscopy and in the solid state by X-ray diffraction methods. The two informations are almost identical, with an arrangement of the aromatic rings rather different from that of the putative bioactive conformation of the parent linear dipeptide. This difference points to the importance of conformational effects and is in agreement with the hypothesis that the positive center may be not essential for antagonism.
包括简单二肽Tyr-L-Tic-NH₂在内的[L-Tic₂]肽的δ选择性拮抗作用与Tyr-Tic“识别位点”相关。为了获取有关Tyr-Tic部分构象偏好的更多信息，我们对一种环状类似物Tyr-Tic的二酮哌嗪进行了结构研究。对几乎没有阿片样活性的环[-Tyr-Tic-]进行构象研究，也有助于区分两个芳香环和碱性氮在决定拮抗作用中的作用。环[-Tyr-Tic-]的结构已通过核磁共振光谱在278 K的DMSO/水溶液中以及通过X射线衍射方法在固态下解析出来。这两种信息几乎相同，芳香环的排列与母体线性二肽假定的生物活性构象有很大不同。这种差异表明构象效应的重要性，并且与阳性中心可能对拮抗作用并非必需这一假设一致。
