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Reversible PEGylation of peptide YY 3‐36 prolongs its inhibition of food intake in mice
Author(s) -
Shechter Yoram,
Tsubery Haim,
Mironchik Marina,
Rubinstein Menachem,
Fridkin Mati
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.03.044
Subject(s) - pegylation , peptide yy , chemistry , peg ratio , peptide , ethylene glycol , in vivo , food intake , pharmacology , endocrinology , medicine , biochemistry , biology , receptor , polyethylene glycol , neuropeptide , microbiology and biotechnology , organic chemistry , finance , neuropeptide y receptor , economics
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 ∼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 ∼24 h. This long‐acting PYY 3‐36 pro‐drug may serve as an effective means for controlling food intake in humans.