Janecka A, Janecki T, Bowers C Y, Folkers K
Institute for Biomedical Research, University of Texas at Austin.
Int J Pept Protein Res. 1994 Jul;44(1):19-23. doi: 10.1111/j.1399-3011.1994.tb00399.x.
A series of antagonists of the luteinizing hormone releasing hormone (LHRH) with substitutions in position 5 and/or 6 that included acylated lysine or p-aminophenylalanine were synthesized, characterized and tested for antiovulatory activity (AOA) in rats, and histamine releasing activity. Some of these antagonists were considerably more soluble at neutral pH than antagonists like Antide. Of 37 new antagonists, the best physico-chemical and biological properties were found for the following two analogs: NAcDNal-DCpa-DPal-Ser-PicLys-D(PicSar)Lys- Leu-ILys-Pro-DAlaNH2 (named Sartide) and NAcDNal-DCpa-DPal-Ser-Tyr-D(PicSar)Lys-Leu-IL ys-Pro-DAlaNH2. They are both soluble in water, inhibit ovulation completely at 0.5 microgram per rat, and have ED50 values for histamine release of about 30 micrograms/mL.
合成了一系列在第5位和/或第6位有取代基的促黄体生成激素释放激素（LHRH）拮抗剂，这些取代基包括酰化赖氨酸或对氨基苯丙氨酸，对其进行了表征，并在大鼠中测试了抗排卵活性（AOA）和组胺释放活性。其中一些拮抗剂在中性pH下的溶解度比Antide等拮抗剂高得多。在37种新的拮抗剂中，以下两种类似物具有最佳的物理化学和生物学特性：NAcDNal-DCpa-DPal-Ser-PicLys-D(PicSar)Lys-Leu-ILys-Pro-DAlaNH2（命名为Sartide）和NAcDNal-DCpa-DPal-Ser-Tyr-D(PicSar)Lys-Leu-ILys-Pro-DAlaNH2。它们都可溶于水，每只大鼠0.5微克时能完全抑制排卵，组胺释放的ED50值约为30微克/毫升。
