Synthesis and biological activity of substance P C-terminal hexapeptide analogues: structure-activity studies.
The synthesis of six hexapeptide analogues of C-terminal Substance P fragment containing alpha, beta-dehydrophenylalanine (delta Phe) in the position 7 or 8 is described. The effect of the structural changes on the hypotensive activity and antigenic properties of analogues was compared. It was found that substitution of delta Phe in various analogues of C-terminal hexapeptide of Substance P resulted in different effects on the hypotensive activity. The analogues [Glp6, delta Phe7]SP6-11 and [Glp6, delta Phe8]SP6-11 retained 70% and 45% of hypotensive activity of the C-terminal hexapeptide of Substance P, respectively but they showed a completely destroyed antigenic determinant. The analogues containing additionally Sar or His in the position 9 showed a complete lack of both: hypotensive activity and expression of the antigenic determinant of Substance P.
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D007022:Hypotension / Q000139:chemically induced; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology
D013373:Substance P