Synthesis and biological activity of substance P C-terminal hexapeptide analogues: structure-activity studies.
A series of analogues of the C-terminal hexapeptide of substance P, modified at the glutaminyl residue, was synthesized and their relative activities as spasmogens were determined in the guinea pig ileum and rat colon muscularis mucosae preparations in vitro. In general, when compared to SP6-11, the loss of the carboxamide group has little effect on activity in the colon and reduces activity on the ileum. The exception to this is the Orn6 analogue which retains activity on both preparations and is proposed as a useful tool for structure-activity studies. It is concluded that the hydrogen-bonding potential of the position 6 substituent may be an important determinant of biological activity.
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D007202:Indicators and Reagents; D009842:Oligopeptides; D013373:Substance P