کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2007510 | 1066377 | 2007 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: PEGylation of cholecystokinin prolongs its anorectic effect in rats PEGylation of cholecystokinin prolongs its anorectic effect in rats](/preview/png/2007510.png)
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 °C. The anorectic activity was tested in vivo in rats. A single bolus intra-peritoneal 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 non-modified peptide. This effect is most evident for the PEG 10 kDa-CCK-9 conjugate.
Journal: Peptides - Volume 28, Issue 5, May 2007, Pages 1003–1011