SYNTHESIS AND SOME PHARMACOLOGICAL PROPERTIES OF OXYTOCIN AND VASOPRESSIN ANALOGS WITH SARCOSINE OR N-METHYL-L-ALANINE IN POSITION-7
SYNTHESIS AND SOME PHARMACOLOGICAL PROPERTIES OF OXYTOCIN AND VASOPRESSIN ANALOGS WITH SARCOSINE OR N-METHYL-L-ALANINE IN POSITION-7
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DOI：
10.1021/jm00358a018
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发表时间：
1983-01-01
影响因子：
7.3
通讯作者：
SCHWARTZ, IL
中科院分区：
文献类型：
--
作者：
GRZONKA, Z;LAMMEK, B;SCHWARTZ, IL
合成了催产素和精氨酸加压素的八种类似物，其中7位脯氨酸残基被肌氨酸或N-甲基丙氨酸取代；评估了这些类似物的一些药理学特性。在位置1含有β-巯基丙酸残基的肽中，确定了位置1的氨基缺失和位置7的上述取代对这些类似物的生物学性质的影响的加和性。所有类似物均具有有效的[大鼠]抗利尿或子宫活性，并且具有选择性作用。从药理学性质的角度来看，在催产素的7位上取代肌氨酸可得到比取代N-甲基丙氨酸具有更高催产和排乳活性的类似物。在精氨酸-加压素中观察到相反的结构-活性关系，其中就升压活性而言，含N-甲基丙氨酸的类似物比含肌氨酸的类似物更有效，并且如果未脱氨基，则在升压活性方面也更有效；如果未脱氨基，则在抗利尿活性方面也更有效。
Eight analogs of oxytocin and arginine-vasopressin were synthesized, in which the proline residue in position 7 was replaced by either sarcosine or N-methylalanine; some of the pharmacological properties of these analogs were evaluated. In peptides containing a .beta.-mercaptopropionic acid residue in position 1, the additivity of the effects of delection of the amino group in position 1 and of the above-noted replacements in position 7 on biological properties of these analogs was ascertained. All of the analogs were potent in either [rat] antidiuretic or uterine activity and also selective in action. From the point of view of pharmacological properties, substitution of sarcosine in position 7 of oxytocin gave analogs with higher oxytocic and milk-ejecting activities than did the substitution of N-methylalanine. The opposite structure-activity relationship was observed with arginine-vasopressin, where the N-methylalanine-containing analogs were more potent than the sarcosine-containing analogs with respect to pressor activity and also, if not deaminated, with respect to pressor activity and also, if not deaminated, with respect to antidiuretic activity.