强啡肽A-(1-13)类似物的合成及生物活性

用固相多肽合成方法,合成了强啡肽A-(1-13)(I)及其类似物Ala⁸,D-Pro¹⁰]-DYNA-(1-13)-NH₂(II)和D-Ala²,Ala⁸,D-Pro¹⁰]-DYNA-(1-13)-NH2(III),并对其进行了镇痛活性试验和MVD及RVD试验。结果表明,合成产物均有镇痛活性,其中类似物III的镇痛活性是1的3.6倍,RVD试验活性比1强135倍,比已知的k-受体强激动剂U500488强11倍。

SYNTHESIS AND BIOLOICAL ACTIVITY OF DYNORPHINA- (1- 13)A NA LOGS

Dynorphin A-(1-13)(I) and its two analogs were synthesized by solid- phase method. Full y-protected pe pt ides were cl eaved from the resi n w ithHF.The three prod ucts were purified and their analgesis activity (antiwrithing response in mouse) and receptor affinity in mouse vas deferens (MVD)and rabbit vas deferens(RVD)were measured. The biological and pharmacologi-cal results showed that the repldcefment of Gla2,Ile8 and Pro10by D- Ala2, Ala8and D-Pro10caused an increase in analgesic activity , receptor affin ity and selectivity. In analgesia and RVD assay, its activity is 2. 6 times and 1 35 times respectively higher than dynorphin A-(1-13). The structure-activity relationshipe were briefly discussed.