کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10227349 | 442 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A solid-phase PEGylation strategy for protein therapeutics using a potent FGF21 analog
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A solid-phase PEGylation strategy for protein therapeutics using a potent FGF21 analog A solid-phase PEGylation strategy for protein therapeutics using a potent FGF21 analog](/preview/png/10227349.png)
چکیده انگلیسی
Fibroblast growth factor 21 (FGF21) is an endocrine-acting hormone that has the potential to treat metabolic diseases, such as type 2 diabetes and obesity. Development of FGF21 into a therapeutic has been hindered due to its low intrinsic bio-stability, propensity towards aggregation and its susceptibility to in vivo proteolytic degradation. In order to address these shortcomings, we've developed recombinant human FGF21 variants by strategically introducing cysteine residues via site-directed mutagenesis, and have also developed a solid-phase nickel affinity PEGylation strategy, whereby engineered, surface-exposed cysteine residues of immobilized proteins were used as a platform to efficiently and site-selectively conjugate with PEG-maleimide. The engineered PEGylated FGF21 conjugates retained its biological functions, as well as demonstrated an increase in half-life by over 211.3 min. By demonstrating the biological activity of the FGF21 analog as a prototype, we have also provided a “generalized” solid-phase approach to effectively increase serum half-life of protein therapeutics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 35, Issue 19, June 2014, Pages 5206-5215
Journal: Biomaterials - Volume 35, Issue 19, June 2014, Pages 5206-5215
نویسندگان
Lintao Song, Yanlin Zhu, Huiyan Wang, Artur A. Belov, Jianlou Niu, Lu Shi, Yaoyao Xie, Chaohui Ye, Xiaokun Li, Zhifeng Huang,