Bienert M, Albrecht E, Berger H, Klauschenz E, Pleiss U, Niedrich H, Mehlis B
Biochim Biophys Acta. 1983 Dec 13;761(2):183-90. doi: 10.1016/0304-4165(83)90227-1.
Analogs of luteinizing hormone-releasing hormone (LHRH) having higher biological activity than LHRH itself are being mainly used to study the biological effects and the mechanism of action of LHRH. In the present study, conditions for the direct 3H-labelling at the histidine residue of analogs of LHRH were worked out, circumventing the synthesis of precursor peptides for labelling. [D-Phe6,desGly10]-LHRH ethylamide and [D-Ser(But)6,desGly10]-LHRH ethylamide were tritiated by tritium gas and a 10% Pd/Al2O3 catalyst to high specific radioactivities. The labelled peptides are sufficiently stable to be used in biochemical studies. The degradability of the analogs by homogenates of various tissues of rats was compared with that of the native LHRH. The analogs were shown to be distinctly degradable, but to a lower extent. The kidney homogenate degrades the analogs [D-Phe6,desGly10]- and [D-Ser(But)6,desGly10]-LHRH ethylamide with 35 and 50%, respectively, of the velocity observed with LHRH, whereas the degradation velocity of the analogs by a homogenate of the hypothalamus and pituitary is only 10% of that of LHRH. It is suggested that the lower degradability of the analogs at peripheral sites and target sites (pituitary, ovary) explains partly their higher biological activity.
具有比促黄体生成激素释放激素（LHRH）本身更高生物活性的LHRH类似物主要用于研究LHRH的生物学效应和作用机制。在本研究中，制定了在LHRH类似物的组氨酸残基处直接进行³H标记的条件，避免了用于标记的前体肽的合成。[D-苯丙氨酸⁶，去甘氨酸¹⁰]-LHRH乙酰胺和[D-丝氨酸（叔丁基）⁶，去甘氨酸¹⁰]-LHRH乙酰胺通过氚气和10%钯/氧化铝催化剂进行氚化，得到高比放射性。标记的肽具有足够的稳定性，可用于生化研究。将这些类似物在大鼠各种组织匀浆中的降解性与天然LHRH的降解性进行了比较。结果表明，这些类似物明显可降解，但降解程度较低。肾脏匀浆分别以LHRH降解速度的35%和50%降解[D-苯丙氨酸⁶，去甘氨酸¹⁰]-和[D-丝氨酸（叔丁基）⁶，去甘氨酸¹⁰]-LHRH乙酰胺，而下丘脑和垂体匀浆对这些类似物的降解速度仅为LHRH的10%。有人认为，这些类似物在外周部位和靶部位（垂体、卵巢）较低的降解性部分解释了它们较高的生物活性。
