Glycoengineering of Interferon-beta 1a Improves Its Biophysical and Pharmacokinetic Properties
- Authors
- Song, Kyoung; Yoon, In-Soo; Kim, Nam Ah; Kim, Dong-Hwan; Lee, Jongmin; Lee, Hee Jung; Lee, Saehyung; Choi, Sunghyun; Choi, Min-Koo; Kim, Ha Hyung; Jeong, Seong Hoon; Son, Woo Sung; Kim, Dae-Duk; Shin, Young Kee
- Issue Date
- 23-May-2014
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.9, no.5
- Journal Title
- PLOS ONE
- Volume
- 9
- Number
- 5
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/12221
- DOI
- 10.1371/journal.pone.0096967
- ISSN
- 1932-6203
- Abstract
- The purpose of this study was to develop a biobetter version of recombinant human interferon-beta 1a (rhIFN-beta 1a) to improve its biophysical properties, such as aggregation, production and stability, and pharmacokinetic properties without jeopardizing its activity. To achieve this, we introduced additional glycosylation into rhIFN-beta 1a via site-directed mutagenesis. Glycoengineering of rhIFN-beta 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-beta mutein with two N-glycosylation sites at 80th (original site) and at an additional 25th amino acid due to a mutation of Thr for Arg at position 27th of rhIFN-beta 1a. Glycoengineering had no effect on rhIFN-beta ligand-receptor binding, as no loss of specific activity was observed. R27T showed improved stability and had a reduced propensity for aggregation and an increased half-life. Therefore, hyperglycosylated rhIFN-beta could be a biobetter version of rhIFN-beta 1a with a potential for use as a drug against multiple sclerosis.
- Files in This Item
-
- Appears in
Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.