[Cyclic analogs of substance P. III. Cyclo (6(sup)gamma----oligomethylenediamine----11) substance P(6-11)-hexapeptides].
Cyclic analogues of substance P of the formula cyclo-[Glu-Phe-Phe-Gly-Leu-Met-NH(CH2)nNH-], where n = 3-10, 12, and open-chain analogues (XVIIIa, b) H-Glu.(NHR)-Phe-Phe-Gly-Leu-Met-NHR, where R = -CH3, -CH2CH2CH3, were synthesized. By NMR spectroscopy it was found that cyclo-compounds with n = 3-8 have regularly arranged structures, stabilized by intramolecular hydrogen bonds. Substances of this type showed less than or equal to 0.1% of the substance P activity on the guinea pig ileum, but some of them antagonize the natural peptide (for compound with n = 5 IC50 = 3.2.10(-6) M). The open-chain compounds proved to have rather high myotropic activity, viz., 22% (R = -CH3) and 8% (R = -CH2CH2CH3) of the substance P activity.
Mutulis
F K
FK
Mutule
I E
IE
Maurops
G Kh
GKh
Bergmann
Iu
Iu
Myshliakova
N V
NV
Strazda
G M
GM
Liepin'sh
E E
EE
Saulitis
Iu B
IuB
Grigor'eva
V D
VD
Balodis
Iu Iu
IuIu
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology; D011487:Protein Conformation; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors
D010456:Peptides, Cyclic; D013373:Substance P
Tsiklicheskie analogi veshchestva P. III. Cyclo(6(sup)gamma----oligometilendiamin----11) veshchestvo P(6-11)-geksapeptidy.