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从几种南美蛙皮所提取的蛙皮啡肽(Dermor-phin,H-酪-D-丙-苯丙-甘-酪-脯-丝-NH_2)显示高效的吗啡样活性。其构-效关系表明,N-端四肽-H-酪-D-丙-苯丙-甘-NH_2(1)是活性所需的最小片段,而(1)在体内外试验中比蛙皮啡肽活性低和作用时间短,这可能由于被羧肽酶迅速酶解所致。为了获得更稳定而强效的衍生物,作者合成16个C端带有不同酰胺的四肽,希望在末端胺酰部分用大体积的疏水基团取代后有利于透过血脑屏障而增强镇痛活性。
Dermor-phin extracted from several South American frogs showed high potency in morphine-like activity. Its structure-activity relationship shows that N-terminal tetrapeptide-H-D-C-Phe-Gan-NH2 (1) is the smallest fragment required for activity, The low activity and short duration of action of the enkephalins may be due to the rapid enzymatic hydrolysis of carboxypeptidases. In order to obtain more stable and potent derivatives, the authors synthesized 16 C-terminal tetrapeptides with different amides. It is hoped that after the terminal amine moiety has been replaced by a bulky hydrophobic group, the transfection of the BBB will be enhanced and the town will be enhanced Pain activity.