Folkers K, Hörig J, Rampold G, Lane P, Rosell S, Björkroth U
Acta Chem Scand B. 1982;36(6):389-95. doi: 10.3891/acta.chem.scand.36b-0389.
The agonist/antagonist activities of four background analogs of substance P (SP) facilitated design and synthesis of 12 new analogs to achieve effective antagonists. (D-Pro2, D-Phe7, D-Trp9)-SP, (D-Pro2, D-Trp7,9)-SP and (D-Arg1, D-Phe7, D-Trp9)-SP showed no agonist activity; 9 analogs showed weak agonist activity of SP. (D-Pro2, D-Trp7,9)-SP was the most potent antagonist which at a concentration of 10(-5) required a 3-fold increase in SP to allow a 50% response by SP. (D-Pro2, Lys6, D-Phe7)-SP and (D-Pro2, D-pClPhe7, D-Trp9)-SP were also potent, and the antagonism was competitive. For specific pairs of peptides, Lys6 is a promising substituent. D-Trp7,9 was as effective as Lys6, D-Phe7. D-pClPhe7 was three times as effective as D-Phe7. D-Dln6 was 1.33-fold better than D-Gln5. D-Pro2 and D-Pro4 were equally effective. D-Pro2 was 1.5 times as effective as D-Lys3. D-Pro2 may not be important. D-pClPhe9 and D-Trp9 were equally effective.
P物质（SP）的四种背景类似物的激动剂/拮抗剂活性有助于设计和合成12种新的类似物以获得有效的拮抗剂。（D-脯氨酸2，D-苯丙氨酸7，D-色氨酸9）-SP、（D-脯氨酸2，D-色氨酸7,9）-SP和（D-精氨酸1，D-苯丙氨酸7，D-色氨酸9）-SP无激动剂活性；9种类似物表现出较弱的SP激动剂活性。（D-脯氨酸2，D-色氨酸7,9）-SP是最有效的拮抗剂，在浓度为10^(-5)时，需要将SP的浓度提高3倍才能使SP产生50%的反应。（D-脯氨酸2，赖氨酸6，D-苯丙氨酸7）-SP和（D-脯氨酸2，D-对氯苯丙氨酸7，D-色氨酸9）-SP也很有效，且拮抗作用具有竞争性。对于特定的肽对，赖氨酸6是一个有前景的取代基。D-色氨酸7,9与赖氨酸6、D-苯丙氨酸7的效果相同。D-对氯苯丙氨酸7的效果是D-苯丙氨酸7的三倍。D-二氨基己酸6比D-谷氨酰胺5好1.33倍。D-脯氨酸2和D-脯氨酸4效果相同。D-脯氨酸2的效果是D-赖氨酸3的1.5倍。D-脯氨酸2可能并不重要。D-对氯苯丙氨酸9和D-色氨酸9效果相同。
