Kitajima Y, Catt K J, Chen H C
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Biochem Biophys Res Commun. 1989 Mar 31;159(3):893-8. doi: 10.1016/0006-291x(89)92192-x.
The biological activities of a series of dimeric analogs of des-Gly10-[D-Lys6]GnRH-NHEt cross-linked at Lys6 by malonic acid and elongated by Gly, i.e., HO-Glyn-CO-CH2-CO-Glyn-OH (n = 0, 1, 2), were analyzed in vitro and in vivo. All three dimeric analogs displayed increased activity in receptor binding and in LH release assays than the original monomer, and dimer Ib (n = 1) showed the highest potency in vitro. This compound also showed the highest activity in the in vivo postcoital assay, in which GnRH agonist potency is measured by inhibition of pregnancy. These results indicate that GnRH receptor activation is substantially enhanced by dimerization of the agonist ligand.
一系列通过丙二酸在赖氨酸6处交联并由甘氨酸延长的去甘氨酸10-[D-赖氨酸6]GnRH-NHEt二聚体类似物，即HO-Glyn-CO-CH2-CO-Glyn-OH（n = 0、1、2）的生物活性，在体外和体内进行了分析。所有三种二聚体类似物在受体结合和促黄体生成素释放试验中均显示出比原始单体更高的活性，并且二聚体Ib（n = 1）在体外表现出最高的效力。该化合物在体内交配后试验中也显示出最高的活性，在该试验中通过抑制妊娠来测量GnRH激动剂的效力。这些结果表明，激动剂配体的二聚化可显著增强GnRH受体的激活。
