A new, potent urotensin II receptor peptide agonist containing a Pen residue at the disulfide bridge

Paolo Grieco; Alfonso Carotenuto; Pietro Campiglia; Enrico Zampelli; Riccardo Patacchini; Carlo A Maggi; Ettore Novellino; Paolo Rovero

doi:10.1021/jm025549i

A new, potent urotensin II receptor peptide agonist containing a Pen residue at the disulfide bridge

J Med Chem. 2002 Sep 26;45(20):4391-4. doi: 10.1021/jm025549i.

Authors

Paolo Grieco¹, Alfonso Carotenuto, Pietro Campiglia, Enrico Zampelli, Riccardo Patacchini, Carlo A Maggi, Ettore Novellino, Paolo Rovero

Affiliation

¹ Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, I-80131 Naples, Italy.

PMID: 12238917
DOI: 10.1021/jm025549i

Abstract

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.

MeSH terms

Animals
Binding, Competitive
CHO Cells
Cricetinae
Cysteine / chemistry
Disulfides / chemistry*
Humans
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation
Oligopeptides / chemical synthesis*
Oligopeptides / chemistry
Oligopeptides / pharmacology
Penicillamine / chemistry*
Peptides, Cyclic / chemical synthesis*
Peptides, Cyclic / chemistry
Peptides, Cyclic / pharmacology
Radioligand Assay
Receptors, Cell Surface / agonists*
Receptors, G-Protein-Coupled*
Structure-Activity Relationship

Substances

Disulfides
Oligopeptides
Peptides, Cyclic
Receptors, Cell Surface
Receptors, G-Protein-Coupled
UTS2R protein, human
aspartyl-cyclo(penicillamyl-phenylalanyl-tryptophyl-lysyl-tyrosyl-cysteinyl)valine
Penicillamine
Cysteine