Novel selective neuropeptide Y2 receptor PEGylated peptide agonists reduce food intake and body weight in mice.
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.
Lumb
Kevin J
KJ
Department of Research Technologies, Bayer Pharmaceuticals Corporation, 400 Morgan Lane, West Haven, Connecticut 06516, USA. kevin_lumb@yahoo.com
DeCarr
Lynn B
LB
Milardo
Lucinda F
LF
Mays
Michelle R
MR
Buckholz
Thomas M
TM
Fisk
Stephen E
SE
Pellegrino
Carla M
CM
Ortiz
Astrid A
AA
Mahle
Cathy D
CD
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
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