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.
MeSH terms
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Animals
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Anti-Obesity Agents / chemical synthesis*
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Anti-Obesity Agents / chemistry
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Anti-Obesity Agents / pharmacology
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Body Weight / drug effects*
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Cyclic AMP / biosynthesis
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Eating / drug effects*
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology
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Peptide YY / chemistry*
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Peptide YY / pharmacology
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Polyethylene Glycols / chemistry*
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Radioligand Assay
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Receptors, Neuropeptide Y / agonists*
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Structure-Activity Relationship
Substances
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Anti-Obesity Agents
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Oligopeptides
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Peptide Fragments
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Receptors, Neuropeptide Y
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neuropeptide Y2 receptor
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Peptide YY
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peptide YY (3-36)
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Polyethylene Glycols
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Cyclic AMP