کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485598 | 1114361 | 2011 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Noncovalent Pegylation by Dansyl-Poly(ethylene Glycol)s as a New Means Against Aggregation of Salmon Calcitonin
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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![عکس صفحه اول مقاله: Noncovalent Pegylation by Dansyl-Poly(ethylene Glycol)s as a New Means Against Aggregation of Salmon Calcitonin Noncovalent Pegylation by Dansyl-Poly(ethylene Glycol)s as a New Means Against Aggregation of Salmon Calcitonin](/preview/png/2485598.png)
چکیده انگلیسی
During all stages of protein drug development, aggregation is one of the most often encountered problems. Covalent conjugation of poly(ethylene glycol) (PEG), also called PEGylation, to proteins has been shown to reduce aggregation of proteins. In this paper, new excipients based on PEG are presented that are able to reduce aggregation of salmon calcitonin (sCT). Several PEG polymers consisting of a hydrophobic dansyl-headgroup attached to PEGs of different molecular weights have been synthesized and characterized physicochemically. After addition of dansyl-methoxypoly(ethylene glycol) (mPEG) 2 kDa to a 40 times molar excess of sCT resulted in an increase in dansyl-fluorescence and a decrease in 90° light scatter suggesting possible interactions. The aggregation of sCT in different buffer systems in presence or absence of the different dansyl-PEGs was measured by changes in Nile red fluorescence and turbidity. Dansyl-mPEG 2 kDa in a 1:1 molar ratio to sCT strongly reduced aggregation. Reduction of sCT aggregation was also measured for the bivalent dansyl-PEG 3 kDa in a 1:1 molar ratio. Dansyl-mPEG 5 kDa deteriorated sCT aggregation. Potential cytotoxicity and hemolysis were investigated. This paper shows that dansyl-PEGs are efficacious in reducing aggregation of sCT.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 5, May 2011, Pages 1648-1662
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 5, May 2011, Pages 1648-1662
نویسندگان
Claudia Mueller, Martinus A.H. Capelle, Tudor Arvinte, Emek Seyrek, Gerrit Borchard,