Structure–activity relationship study of position 4 in the urotensin-II receptor ligand U-II(4-11)

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2008-05, Vol.29 (5), p.674-679
• Main Authors: Marzola, Erika, Camarda, Valeria, Batuwangala, Madura, Lambert, David G., Calo’, Girolamo, Guerrini, Remo, Trapella, Claudio, Regoli, Domenico, Tomatis, Roberto, Salvadori, Severo
• Format: Article
• Language: English
• Subjects: Amino Acids - chemistry; Amino Acids - metabolism; Animals; Aorta - anatomy & histology; Aorta - physiology; Calcium - metabolism; Cell Line; HEK293 rUT; Humans; Ligands; Male; Molecular Structure; Muscle Contraction - physiology; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - metabolism; Rat aorta; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - metabolism; Structure-Activity Relationship; Structure–activity study; Urotensin II; Urotensins - chemistry; Urotensins - genetics; Urotensins - metabolism; UT receptor; Vasoconstriction - physiology
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2007.07.025

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.