Structure-activity relationship study of position 4 in the urotensin-II receptor ligand U-II(4-11).
In the present study we describe the synthesis and biological evaluation of 24 analogues of the urotensin II (U-II) fragment U-II(4-11) substituted in position 4 with coded and non-coded aromatic amino acids. All of the new analogues behaved as full U-II receptor (UT) agonists. Our results indicated that aromaticity is well tolerated, size, length and chirality of the side chain are not important, while substituents with a nitrogen atom are preferred. Thus acylation of U-II(5-11) with small groups bearing nitrogen atoms could be instrumental in future studies for the identification of novel potent UT receptor ligands.
Marzola
Erika
E
Department of Pharmaceutical Sciences and Biotechnology Center, Section of Pharmacology, University of Ferrara, 44100 Ferrara, Italy.
Camarda
Valeria
V
Batuwangala
Madura
M
Lambert
David G
DG
Calo'
Girolamo
G
Guerrini
Remo
R
Trapella
Claudio
C
Regoli
Domenico
D
Tomatis
Roberto
R
Salvadori
Severo
S
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D013329:Structure-Activity Relationship; D014579:Urotensins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology