Reversible PEGylation of peptide YY_3-36 prolongs its inhibition of food intake in mice

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• 作者：Shechter ; Yoram ; Tsubery ; Haim ; Mironchik ; Marina ; Rubinstein ; Menachem ; Fridkin ; Mati
• 关键词：Peptide pro-drug ; Long-acting peptide ; Fluorenyloxycarbonyl linker ; Satiety
• 刊名：FEBS Letters
• 出版年：2005
• 出版时间：April 25, 2005
• 年：2005
• 卷：579
• 期：11
• 页码：2439-2444
• 全文大小：192 K

文摘

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 (PEG₄₀–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.