酪氨酸相关肽的合成及抗孕酮生成活性

SYNTHESIS OF TYKOSINE-RELATED PEPTIDE AND THEIR EFFECT ON PROGESTERONE PRODUCTION DX

利用固相法合成了二十个含羟基氨基酸的小肽。其中，以０．５ｍｏｌ·Ｌ－１二甲二氯硅烷／１．５ｍｏｌ·Ｌ－１苯酚／ＤＣＭ＊为脱除Ｂｏｃ试剂，以ＴＦＭＳＡ为切除树脂试剂。经Ｃ－１８反相柱纯化后，全部产物均通过氨基酸分析要求。体外黄体细胞分泌孕酮实验表明有八个肽化物ＧｌｙＴｙｒＡｌａＬｙｓ，（ＳａｒＳｅｒ）２Ｌｙｓ及其申酯，ＴｙｒＬｙｓ，ＨｉｓＴｙｒ－ＮＨ２，ＴｈｒＰｒｏＴｙｒＬｙｓ－ＮＨ２，ＴｙｒＴｈｒＰｒｏＡｒｇＬｙｓ，ＡｓｐＨｉｓＰｒｏＴｈｒ－ＰｈｅＬｙｓ显示较强的抑制ｈＣＧ致孕酮分泌的活性，而且前三个肽还能显著抑制基础孕酮的分泌，相反，ＧｌｙＳｅｒＴｙｒ能刺激基础孕酮的分泌。目前尚未建立合理的结构一活性关系。

Twenty peptides containing hydroxy- amino acids have been synthesized manually by stepwise solid-phase procedure.The chloromethyl resin and MBHA resin were used as solid supports.A new reagent of 0.5 mol·L-1 DDSi/1.5mol·L-1 phenol/ DCM was applied for the removal of Na-Boc group.TFMSA was the cleaving reagent.After purification by C-18 column,allproducts were assayed according to amino acid analysis·The bioactivity of synthetic peptides was tested for the effect on progesterone production in uitro.Eight peptides, GlyTyrAiaLys,( SarSer )2Lys and its metftyl ester,TyrLys,HisTyr-NH2,ThrProTyrLys-NH2 TyrThrProArgLys and AspHisProThrPheLys showed significant effect on inhibiting hCG-induced progesterone production,and first three of them could also inhibit basal progesterone secretion. However,peptide GlySerTyr exhibited stimulative activity on basal proges- erone secretion,So far,no reasonable relationship between structure and bioactivity was found。