Metabolism of peptide YY 3-36 in Göttingen mini-pig and rhesus monkey

Peptides
Jørgen OlsenRasmus Jorgensen

Abstract

Peptide YY 3-36-amide (PYY3-36) is a peptide hormone, which is known to decrease appetite and food-intake by activation of the Y2 receptor. The current studies were designed to identify the metabolites of PYY3-36 in mini-pig and rhesus monkey. Plasma samples were analyzed by high resolution LC-MS (and MS/MS) in order to unambiguously identify the metabolites of PYY3-36. In summary, the metabolism of PYY3-36 was similar in mini-pig and rhesus monkey. Several metabolites were identified and PYY3-34 was identified at the highest levels in plasma. In addition, mini-pigs were also dosed with PYY1-36-amide, PYY3-35, PYY3-34 and [N-methyl 34Q]-PYY3-36-amide in order to investigate the mechanisms by which PYY was metabolized. PYY3-35 was rapidly converted to PYY3-34 whereas dosing of PYY3-34 to mini-pigs only showed circulating degradation products at low levels, i.e., PYY3-34 was metabolically more stable than PYY3-36 and PYY3-35. [N-methyl 34Q]-PYY3-36-amide was hypothesized to be stable toward cleavage between 34Q and 35R and after i.v. administration to mini-pigs, one major cleavage product was identified as [N-methyl 34Q]-PYY3-35. Overall, this showed that cleavage between 35R and 36Y was possible as well as between 34Q and 35R (a...Continue Reading

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Citations

May 2, 2019·Drug Development and Industrial Pharmacy·Jie ShaoGuenther Hochhaus
Jul 2, 2019·Biomedical Chromatography : BMC·Lijuan KangWenying Jian
Jul 16, 2020·Chembiochem : a European Journal of Chemical Biology·Panagiota KalomoiriKnud J Jensen
Jan 5, 2021·Current Opinion in Endocrinology, Diabetes, and Obesity·Ryan A LaffertyNigel Irwin
Jan 16, 2021·Angewandte Chemie·Søren ØstergaardBirgitte S Wulff
Jul 18, 2021·Pharmaceutical Research·Christian PoulsenSøren Østergaard
Nov 7, 2018·Journal of Medicinal Chemistry·Søren ØstergaardBirgitte S Wulff
Jul 17, 2019·Molecular Pharmaceutics·Esben M BechKnud J Jensen

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