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Title: PEGylation of cholecystokinin prolongs its anorectic effect in rats
Authors: Leon-Tamariz, Fabian ×
Verbaeys, Isabelle
Van Boven, Maurits
De Cuyper, Marcel
Buyse, Johan
Clynen, Elke
Cokelaere, Marnix #
Issue Date: May-2007
Publisher: Elsevier science inc
Series Title: Peptides vol:28 issue:5 pages:1003-1011
Abstract: The anorectic compound CCK-9 was coupled to polyethylene glycol 5 kDa, 10 kDa, 20 kDa and 30 kDa., under different reaction conditions. Conjugates were purified by HPLC and characterized by MALDI-TOF MS. A 96% PEGylation yield was obtained in buffer pH 7.5 after 6 h reaction at 20 degrees C. The anorectic activity was tested in vivo in rats. A single bolus intraperitoneal injection of non-modified CCK-9 resulted in a significant initial food intake reduction 30 min after food presentation (87% compared to paired control group). When PEG-CCK-9 conjugates modified with polymers of molecular weight up to 20 kDa were injected, lower but statistically significant initial food intake reductions were obtained (76% for PEG 10 kDa-CCK-9 conjugate compared to control group). The cumulative food intake reduction of non-modified CCK-9 is normalized within 1-2 h, whereas the PEG-CCK-9 molecules showed a prolonged anorectic activity lasting for 6 h for PEG 5 kDa-CCK-9; 23 h for PEG 10 kDa-CCK-9 and between 8 h and 23 h for PEG 20 kDa-CCK-9. For PEG 30 kDa-CCK-9 conjugate, neither an initial nor a cumulative FI reduction was observed. PEG-CCK-9 conjugates show a significantly prolonged anorectic activity in comparison to the nonmodified peptide. This effect is most evident for the PEG 10 kDa-CCK-9 conjugate. (c) 2007 Elsevier Inc. All rights reserved.
URI: 
ISSN: 0196-9781
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
Anatomy, Kulak (-)
Toxicology and Pharmacology
Division of Livestock-Nutrition-Quality (-)
Animal Physiology and Neurobiology Section - miscellaneous
× corresponding author
# (joint) last author

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