title: A long-acting selective neuropeptide Y2 receptor PEGylated peptide agonist reduces food intake in mice.
abstract: Activation of the NPY2 receptor to reduce appetite while avoiding activation of the NPY1 and NPY5 receptors that stimulate feeding provides a pharmaceutical approach to modulate food intake. The naturally occurring peptide and development candidate PYY(3-36) is a non-selective NPY1, NPY2, and NPY5 agonist of limited in vivo duration of action. N-terminal modification with 20 kDa PEG of a selective NPY2 receptor agonist peptide results in a long-acting agent that outperforms PYY(3-36) in reducing food intake in mice. The results suggest that PEGylated, selective NPY2 peptide agonists offer a significantly improved therapeutic benefit over PYY(3-36) for obesity management.
authors.affiliation: Department of Metabolic Disorders Research, Bayer Pharmaceuticals Corporation, 400 Morgan Lane, West Haven, CT 06516, USA.
authors.forename: Lynn B
authors.initials: LB
authors.lastname: DeCarr
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Buckholz
authors.forename: Lucinda F
authors.initials: LF
authors.lastname: Milardo
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mays
authors.forename: Astrid
authors.initials: A
authors.lastname: Ortiz
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Lumb
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008968:Molecular Conformation; D010446:Peptide Fragments; D019894:Peptide YY / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D017476:Receptors, Neuropeptide Y / Q000737:chemistry*
chemical_list: D010446:Peptide Fragments; D010455:Peptides; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); D011092:Polyethylene Glycols