Reversible PEGylation of peptide YY3‐36 prolongs its inhibition of food intake in mice
- 31 March 2005
- journal article
- Published by Wiley in FEBS Letters
- Vol. 579 (11) , 2439-2444
- https://doi.org/10.1016/j.febslet.2005.03.044
Abstract
Administration of peptide YY(3-36) (PYY(3-36)) to fasting humans or mice shortly before re-feeding effectively reduced their food intake, but PYY(3-36) exhibited a functional half-life of only approximately 3 h. Attachment of poly(ethylene glycol) to proteins and peptides (PEGylation) prolongs their half-life in vivo, but completely inactivated PYY(3-36). We developed a reversibly PEGylated PYY(3-36) derivative by coupling it to a 40 kDa PEG through a spontaneously cleavable linker. The resulting conjugate (PEG(40)-FMS-PYY(3-36)) gradually released unmodified PYY(3-36) in vivo, exhibiting an eightfold increase in its functional half-life, to approximately 24h. This long-acting PYY(3-36) pro-drug may serve as an effective means for controlling food intake in humans.Keywords
This publication has 24 references indexed in Scilit:
- Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in ratsAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2004
- Does gut hormone PYY3–36 decrease food intake in rodents?Nature, 2004
- Inhibition of Food Intake in Obese Subjects by Peptide YY3–36New England Journal of Medicine, 2003
- Peptide and protein PEGylation: a review of problems and solutionsPublished by Elsevier ,2001
- A new approach for prolonging the half-life of peptides, proteins and low-molecular-weight drugs in vivoDrugs of the Future, 2001
- Drug Delivery Systems Employing 1,4- or 1,6-Elimination: Poly(ethylene glycol) Prodrugs of Amine-Containing CompoundsJournal of Medicinal Chemistry, 1999
- Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body WeightEndocrine Reviews, 1999
- The clinical efficacy of poly(ethylene glycol)-modified proteinsJournal of Controlled Release, 1990
- The preparation and properties of novel reversible polymer‐protein conjugates 2‐ω‐Methoxypolyethylene (5000) glycoxymethylene‐3‐methylmaleyl conjugates of plasminogen activatorsFEBS Letters, 1987