A synthetic glycopeptide of substance P analogue (SP6-11) with enhanced NK-1 receptor specificity.
A new glycopeptide analogue of substance P (6-11) (SP6-11), namely, N1,6 (beta-D-glucopyranosyl) [Glu6, Pro9]SP6-11, has been synthesized and found to be water soluble. The in vitro biological activity of this glycopeptide was determined for spasmogenic activity in the guinea pig ileum and for potentiation of electrically evoked contractions in the rat vas deferens. Thus, activities on NK-1, NK-2, and NK-3 receptor types have been differentiated by two assays and, in the case of NK-1 and NK-3, receptors in guinea pig ileum (GPI) were assayed using specific pharmacological procedures. The ED50 values for the analogue and reference peptides substance P (SP), neurokinin A(NKA), and neurokinin B (NKB) were determined and potencies relative to SP were calculated. The analogue is three times more potent than the potent NK-1 agonist SP on NK-1 receptors. Moreover, this glycopeptide proved to be as selective for the NK-1 receptor as the specific agonist SPOMe (the methyl ester of substance P).
Haro
I
I
Laboratory of Peptides, Biological Organic Chemistry Department, Barcelona, Spain.
Busquets
M A
MA
Torres
J L
JL
Valencia
G
G
Garcia-Anton
J M
JM
Reig
F
F
D000818:Animals; D002855:Chromatography, Thin Layer; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D018039:Receptors, Tachykinin; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
D010446:Peptide Fragments; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; C063325:substance P (6-11), N(1,6)(beta-glucopyranosyl)Glu(5)-Pro(9)-; D013373:Substance P