Synthesis and biological activity of N-methylated analogues of neurokinin A.
Limited conformational constraints have been introduced in the sequence of the C-terminal heptapeptide NKA(4-10) by N-methylation of individual peptide bonds and the biological activities of the peptides thus obtained were evaluated on three in vitro preparations sensitive and quite selective for each of the naturally-occurring neurokinins, in order to assess the effect of N-methylation on receptor selectivity. The analogue methylated in position 7, namely [MeVal7] NKA(4-10) shows some selectivity for the NK-P receptor, while none of the tested compounds appear to be selective for the NK-A receptor.
Rovero
P
P
Chemistry Department, A. Menarini Laboratories, Firenze, Italy.
Pestellini
V
V
Patacchini
R
R
Santicioli
P
P
Maggi
C A
CA
Meli
A
A
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A; D009479:Neuropeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011169:Portal Vein / Q000502:physiology; D051381:Rats; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000502:physiology
D009479:Neuropeptides; D015288:Neurokinin A