Identification of new agonists of urotensin-II from a cyclic peptide library.
Urotensin-II (UT-II) is thought to be involved in the regulation of cardiovascular homeostasis and pathology. A head-to-tail cyclic hexapeptide library based on UT-II sequence was designed, synthesized, and evaluated by the activity on the UT-II receptor (GPR-14). A new synthetic sequence, WK[Xaa] (Xaa: amino acid with aromatic side chain), was identified as a characteristic minimum fragment activating hUT-II receptor instead of the WK[Y] sequence. Compound 1 showed an agonistic activity with an EC(50) value of 6.94 nM. The conformational investigation suggested that 1 did not have typical secondary structure in the message sequence. Structural analyses may enable us to investigate the active conformation of UT-II and lead to the identification of new ligands for GPR-14.
Odagami
Takenao
T
Research and Development, PRISM Bio. Lab. Corporation. 4259-3, Nagatsuta-cho, Midori-ku, Yokohama 226-8510, Japan.
Tsuda
Yuko
Y
Kogami
Yuji
Y
Kouji
Hiroyuki
H
Okada
Yoshio
Y
D000595:Amino Acid Sequence; D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism*; D014579:Urotensins / Q000737:chemistry*
D019151:Peptide Library; D010456:Peptides, Cyclic; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II