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目的运用合成的 VIP/PACAP 相关肽,在离体豚鼠胆囊探讨 PACAP 的结构与生物活性的相关性.方法用多品种同时氨基酸固相合成仪 Fmoc 法高效合成 VIP,PACAP 及其相关肽.用改良水平浴槽法测定比较各多肽对离体豚鼠胆囊的生物效应.结果 VIP 引起豚鼠胆囊平滑肌的舒张;与此相反,PACAP27则呈收缩效应,改变第4、第5和第24-26位氨基酸残基,对其生物效应没有明显影响.尽管[Leu~(13)]-PACAP27,是一个在α螺旋区域的变构体,但其收缩胆囊的活性并没有明显降低(P>0.05),而且较[Gly~8]-,[DAsp~8]-PACAP27和第21位的3个置换物更强.Des-[His~1]和[Ala~6]-PACAP27在10~(-7)mol/L 的浓度时未见生物活性,[Gly~8]-,[DAsp~8]-,[Phe~(21)]-和[Pro~(21)]-PACAP27在该浓度时收缩效应仅相当于 PACAP27的25%(P<0.05).结论在对豚鼠胆囊平滑肌的生物活性方面,PACAP27的 N 端(第1-8位)氨其酸残基较其他区域更为重要.
Objective To explore the relationship between the structure and biological activity of PACAP in vitro using synthetic VIP / PACAP-related peptide.Methods VIP, PACAP and its related peptides were synthesized efficiently by Fmoc method using a variety of simultaneous amino acid solid phase synthesizers, The results of the comparison of the biological effects of each peptide on the isolated gallbladder of guinea pigs by the horizontal bath method showed that VIP induced the relaxation of the gallbladder smooth muscle in guinea pigs. Contrary to this, PACAP27 showed a contraction effect and changed the amino acid residues 4, 5 and 24-26 Had no significant effect on its biological effects.Although [Leu ~ (13)] - PACAP27, an a-helical domain variant, did not significantly reduce the activity of contracting gallbladder (P> 0.05) Gly ~ 8] -, [DAsp ~ 8] -PACAP27 and three substitutions at position 21.Des- [His ~ 1] and [Ala ~ 6] -PACAP27 are more stable at 10 ~ (-7) mol / L No significant difference was observed in the concentration of [Gly ~ 8] -, [DAsp ~ 8] -, [Phe ~ (21)] - and [Pro ~ (21)] - PACAP27 at this concentration. (P <0.05) .Conclusion The amino acid residues of PACAP27 at the N terminus (1-8) are more important than other regions in the biological activity of guinea pig gallbladder smooth muscle.