A new, potent urotensin II receptor peptide agonist containing a Pen residue at the disulfide bridge.
Replacing Cys(5) by Pen (penicillamine, beta,beta-dimethylcysteine) in the cyclic C-terminal U-II octapeptide, U-II(4-11), we have obtained a potent urotensin II (U-II) receptor agonist. Conformational analysis of solution NMR data indicated that the putative biologically active conformation of U-II is stabilized by introduction of a Pen residue. To the best of our knowledge, this is the most potent U-II receptor agonist reported to date.
Grieco
Paolo
P
Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, I-80131 Naples, Italy.
Carotenuto
Alfonso
A
Campiglia
Pietro
P
Zampelli
Enrico
E
Patacchini
Riccardo
R
Maggi
Carlo A
CA
Novellino
Ettore
E
Rovero
Paolo
P
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010396:Penicillamine / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000819:agonists*; D043562:Receptors, G-Protein-Coupled; D013329:Structure-Activity Relationship
D004220:Disulfides; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; C466635:aspartyl-cyclo(penicillamyl-phenylalanyl-tryptophyl-lysyl-tyrosyl-cysteinyl)valine; D010396:Penicillamine; D003545:Cysteine