Pyridoxal-5'-phosphate derivatives of substance P: preparation, spasmogenic activity, and degradation by human plasma.
Two fluorescent derivatives of substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) were prepared by chemical modification of the native peptide by pyridoxal-5'-phosphate (pyridoxal-P). The formation of both pyridoxal-P-derivatives of SP is the result of one modification procedure. The determination of the amino acid composition showed that in one of the derivatives the epsilon-amino group of the Lys residue [epsilon-(P-pxy)-SP] and in the other the epsilon-amino group of the Lys residue and also the N-terminal amino group [alpha, epsilon-di-(P-pxy)-SP] of SP had been substituted by pyridoxal-P. epsilon-(P-pxy)-SP and alpha, epsilon-di-(P-pxy)-SP have spasmogenic activity with ED50 of 1.8 X 10(-9) and 4 X 10(-9) M, respectively, tested on isolated guinea pig ileum. The fluorescence of P-pxy residues permits detection of as little as 1 pmol/ml of epsilon-(P-pxy)-SP and 0.5 pmol/ml of alpha, epsilon-di-(P-pxy)-SP. Both analogues of SP obtained are degraded by human plasma more slowly than the native peptide.
Akopyan
T
T
Arzumanyan
A
A
Aghajanyan
H
H
Arutunyan
A
A
Khanazadyan
A
A
D000818:Animals; D001711:Biotransformation; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013057:Spectrum Analysis; D013268:Stimulation, Chemical; D013373:Substance P / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology
C048428:substance P, pyridoxal-phosphate(6)-Lys(3)-; C048429:substance P, alpha-N-Arg(1)-epsilon-N-Lys(3)-di-(pyridoxal phosphate)-; D013373:Substance P