title: Glycoengineering of interferon-β 1a improves its biophysical and pharmacokinetic properties.
abstract: The purpose of this study was to develop a biobetter version of recombinant human interferon-β 1a (rhIFN-β 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-β 1a via site-directed mutagenesis. Glycoengineering of rhIFN-β 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-β 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-β 1a. Glycoengineering had no effect on rhIFN-β 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-β could be a biobetter version of rhIFN-β 1a with a potential for use as a drug against multiple sclerosis.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Research Institute of Reference Biolabs. Inc., Seoul, Republic of Korea.
authors.forename: Kyoung
authors.initials: K
authors.lastname: Song
authors.affiliation: College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam, Republic of Korea.
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Gyeonggi-do, Republic of Korea.
authors.forename: Nam Ah
authors.initials: NA
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: PanGen Biotech Inc., Gyeonggi-do, Republic of Korea.
authors.forename: Jongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Research Institute of Reference Biolabs. Inc., Seoul, Republic of Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Saehyung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Research Institute of Reference Biolabs. Inc., Seoul, Republic of Korea.
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Choi
authors.affiliation: College of Pharmacy, DanKook University, Chungnam, Republic of Korea.
authors.forename: Min-Koo
authors.initials: MK
authors.lastname: Choi
authors.affiliation: Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Ha Hyung
authors.initials: HH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Gyeonggi-do, Republic of Korea.
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, CHA University, Gyeonggi-do, Republic of Korea.
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Son
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shin
mesh_terms: D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D006031:Glycosylation; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000493:pharmacokinetics*; D008024:Ligands; D009005:Monosaccharides / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011487:Protein Conformation; D055550:Protein Stability; D051381:Rats; D012995:Solubility; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D009005:Monosaccharides; D016899:Interferon-beta; D019158:N-Acetylneuraminic Acid; D000068556:Interferon beta-1a