胃泌素类似物的人工合成和泌酸活性研究

本文采用液相合成法合成了九种胃泌素类似物,并用大白鼠胃灌流技术测定其泌酸活性。若以五肽胃泌素(Boc-β-Ala-Trp-Met-Asp-phe-NH_2,Boc-五肽)的泌酸活性为100％,则胃泌其它类似物的活性分别为:Boc-四肽(Boc-Trp-Met-Asp-Phe-NH_2)30.32％,Boc-三肽(Boc-Met-Asp-phe-NH_2)0.13％;Fmoc-五肽(Fmoc-β-Ala-Trp-Met-ASP-Phe-NH_2)171％,Fmoc-四肽(Fmco-Trp-Met-Asp-Phe-NH_2)32.88％,Fmoc-三肽·(Fmoc-Met-Asp-Phe-NH_2)0.17％,五肽·TFA(β-Ala-Trp-Met-Asp-Phe-NH_2·TFA)17.45％,四肽·TFA(Trp-Met-Asp-phe-NH_2·TFA)5.58％。 实验结果显示四肽胃泌素类似物的活性这比三肽的高,表明胃泌素C-端片段中色氨酸残基对泌酸活性十分重要。在胃泌素类似物的N-端导入保护基同样提高它们的生物学活性,而Fmoc-保护基的作用还强于Boc-保护性。推测其主要原因是在N-式加上一个疏水性强的基团后有利于形成一个与受体相结合的活性构象。

The Synthesis of The Gastrin Analogs And Their Stimulation of Gastric Acid Secretion In The Rat

Nine gastrin related peptides were synthesized by the liquid-phase synthesis method. An improved technique of perfusion of the stomach in the rat was used to determine the gastric secretion of these analogs. The potency of gastric secretion of pentagastrin was compared with these analogs in per molar basis. The results showed that the relative potency of pentagastrin, Boc-Trp-Met-Asp-Phe-NH2 Boc-Met-Asp-Phe-NH2, Fmoc-β-Ala-Trp-Met-Asp-Phe-NH2, Fmoc-Trp-Met-Asp--Phe-NH2, Fmoc-Met-Asp-Phe-NH2, β-Ala-Trp-Met-Asp-Phe-NH2 . TFA, and Trp -Met-Asp-Phe-NH2·TFA was 100%, 30.32%, 0.13%, 17%, 32.88%0.17%, 17.45%, 5.58%, respectively.These data indicated that the potency of tetrapeptide was much more active/than that of tripeptides. It suggests the tryptophanyi residue is very important for gastric secretion activity. The potency was also incresed by introduction of a protec ting group at the N-terminus of gastrin derixatives. In particular the Fmoc-protecting group was more ef fect than Boc-protecting group. It may be chiefly due to the com-formation of these gastrin related peptides more suitable for their receptor, after being added a strong hydophobic group.