新皮啡肽I(DELI)类似物的合成及构效关系研究

STUDIES ON THE SYNTHESIS AND STRUCTURE-ACTIVITY RELATION OF DELTORPHIN I ANALOGUES

摘要: 用固相多肽合成法合成了类阿片肽新皮啡肽I(DELI)及其三个类似物(将Asp4从5位到7位逐一后移)。实验发现DELI在离体条件(浓度范围10^-14～10mol·L^-1)和在体条件(剂量范围0.5～5μg·kg^-1)下能提高红细胞玫瑰花环形成细胞百分率(E-RFC)和红细胞C3b受体花环百分率(RBC-CR₁),且可被纳洛酮阻断。这些结果表明DELI能提高大鼠免疫功能。实验还发现DELI及其类似物的镇痛和免疫活性次序(由大到小)分别是Asp⁴,Asp⁷,Asp⁵,Asp⁶和Asp⁴,Asp⁷,Asp⁶,Asp⁵。

Abstract: Endogenous opioid deltorphin I(DEL I)and its three analogues(progressive,stepwise repositioning of Asp from 5 to 7)were synthesized solid phase method. DEL I at 10^-14～10^-10 mol·L^-1 in vitro and at 0.5～5μg·kg^-1 in vivo was found to increase the percentages of erythrocyte rosette forming cells(E-RFC) and red blood cell C3b receptor garland(RBC-CR1).Thisaugmentative effect of DEL I was antagonized by naloxone. The results indicate that DEL I enhancedthe immune function of rats. The order(from strong to weak)of the analgesic and immune activitywas shown to be Asp⁴, Asp⁷, Asp⁵,Asp⁶ and Asp⁴,asp⁷,Asp⁶,Asp⁵ respectively.