Novel Selective Neuropeptide Y2 Receptor PEGylated Peptide Agonists Reduce Food Intake and Body Weight in Mice

• Published in: Journal of medicinal chemistry Vol. 50; no. 9; pp. 2264 - 2268
• Main Authors: Lumb, Kevin J, DeCarr, Lynn B, Milardo, Lucinda F, Mays, Michelle R, Buckholz, Thomas M, Fisk, Stephen E, Pellegrino, Carla M, Ortiz, Astrid A, Mahle, Cathy D
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 03.05.2007
• Subjects: Animals; Anti-Obesity Agents - chemical synthesis; Anti-Obesity Agents - chemistry; Anti-Obesity Agents - pharmacology; Biological and medical sciences; Body Weight - drug effects; Cyclic AMP - biosynthesis; Eating - drug effects; General and cellular metabolism. Vitamins; Humans; Male; Medical sciences; Mice; Mice, Inbred C57BL; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacology; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Peptide YY - chemistry; Peptide YY - pharmacology; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Radioligand Assay; Receptors, Neuropeptide Y - agonists; Structure-Activity Relationship; Agonist; Peptides; Body weight; Selectivity; Pyridine derivatives; Ethylene oxide polymer; Structure activity relation; Subcutaneous administration; Chemical synthesis; Nutritional status; Human; Obesity; Rodentia; Nutrition disorder; In vitro; Y2 neuropeptide Y receptor; In vivo; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Mouse; Food intake; Polypeptide; Animal; Affinity; Benzamide derivatives; Carboxamide; Peptide synthesis; Anorectic; Conjugated compound
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm061454v

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.