新型内皮素受体六肽拮抗剂的设计合成及其生物活性

Syntheses and Bioactivities of Endothelin Receptor Antagonist Hexapeptides

以内皮素 1(endothelin 1,ET 1)羧基末端六肽 (His Leu Asp Ile Ile Trp)为模板 ,应用D型芳香性非天然氨基酸替代六肽结构中His残基进行结构设计 ,利用固相肽合成技术合成新型ET受体肽类拮抗剂 ,得到 12个新六肽化合物。对所得化合物进行拮抗ET 1收缩大鼠胸总动脉的活性研究 ,其中C 1、C 3、C 5、C 7、C 8、C 11等 6个化合物在 10

Based on the structure of hexapeptide(His Leu Asp Ile Ile Trp,16 21) of the C terminal fragment of endothlin 1(ET 1),a series of novel hexapeptide analogues was synthesized using the solid phase peptide synthesis(SPPS) technology by the replacement of the residue His with D type of aromatic unusual amino acids.The introduction of D Phe derivatives in these peptidic ET antagonists resulted in potent ET antagonistic activity.The pectoral artery of the rat mainly contained ET A receptors and few ET B receptors.Six compounds of the twelve hexapeptides against ET 1 showed significant activity under the concentration on 10 -9 mol/L.