Seprodi J, Coy D H, Vilchez-Martinez J A, Pedroza E, Huang W Y, Schally A V
J Med Chem. 1978 Sep;21(9):993-5. doi: 10.1021/jm00207a029.
There is evidence that, in its receptor-binding conformation, the N and C terminus of LH-RH may be in close proximity and two cyclic analogues of the hormone were synthesized to test the hypothesis. Cyclic [beta-Ala1,D-Ala6,Gly10]- and [6-aminohexanoic acid1,D-Ala6,Gly10]-LH-RH were prepared by treatment of their linear precursor peptides with dicyclohexylcarbodiimide in the presence of 1-hydroxybenzotriazole in dilute dimethylformamide solution. Although the linear peptides possessed no detectable LH-releasing activity in ovariectomized rats, the cyclic beta-Ala analogue had 1.2% the activity of LH-RH, whereas the longer chain cyclic 6-aminohexanoic acid analogue had 0.65% activity. These results support the concept of an important interaction between the ends of the LH-RH molecule possibly involving hydrogen-bond formation between the pyrrolidone carbonyl group of pyroglutamic acid and the glycinamide group.
有证据表明，在其受体结合构象中，促黄体生成激素释放激素（LH-RH）的N端和C端可能靠得很近，因此合成了该激素的两种环状类似物来验证这一假说。通过在稀二甲基甲酰胺溶液中，在1-羟基苯并三唑存在的情况下，用二环己基碳二亚胺处理其线性前体肽，制备了环状[β-丙氨酸1，D-丙氨酸6，甘氨酸10]-和[6-氨基己酸1，D-丙氨酸6，甘氨酸10]-LH-RH。尽管线性肽在去卵巢大鼠中没有可检测到的促黄体生成素释放活性，但环状β-丙氨酸类似物具有LH-RH活性的1.2%，而较长链的环状6-氨基己酸类似物具有0.65%的活性。这些结果支持了LH-RH分子末端之间重要相互作用的概念，这种相互作用可能涉及焦谷氨酸的吡咯烷酮羰基与甘氨酰胺基团之间形成氢键。
