title: Novel selective neuropeptide Y2 receptor PEGylated peptide agonists reduce food intake and body weight in mice.
abstract: Selective activation of the NPY2 receptor to suppress appetite provides an approach to obesity management. Selective NPY2 PEGylated peptide agonists are described that consist of a peptide core corresponding to residues 25-36 of PYY and a nonpeptidic moiety at the peptide N-terminus that contributes to in vitro potency and in vivo efficacy and provides a PEGylation site. The lead peptide elicits a dose-dependent reduction of food intake in lean mice and of food intake, body weight, and fat mass in DIO mice.
authors.affiliation: Department of Research Technologies, Bayer Pharmaceuticals Corporation, 400 Morgan Lane, West Haven, Connecticut 06516, USA. kevin_lumb@yahoo.com
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Lumb
authors.forename: Lynn B
authors.initials: LB
authors.lastname: DeCarr
authors.forename: Lucinda F
authors.initials: LF
authors.lastname: Milardo
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mays
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Buckholz
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Fisk
authors.forename: Carla M
authors.initials: CM
authors.lastname: Pellegrino
authors.forename: Astrid A
authors.initials: AA
authors.lastname: Ortiz
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Mahle
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis; D004435:Eating / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D019894:Peptide YY / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011869:Radioligand Assay; D017476:Receptors, Neuropeptide Y / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D019440:Anti-Obesity Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); D011092:Polyethylene Glycols; D000242:Cyclic AMP