Solid-Phase PEGylation of Recombinant Interferon alpha-2a for Site-Specific Modification: Process Performance, Characterization, and in Vitro Bioactivity.

Solid-Phase PEGylation of Recombinant Interferon alpha-2a for Site-Specific Modification: Process Performance, Characterization, and in Vitro Bioactivity. Research Abstract Details 

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Solid-Phase PEGylation of Recombinant Interferon alpha-2a for Site-Specific Modification: Process Performance, Characterization, and in Vitro Bioactivity. Abstract Text:

Byung Kook Lee,Jin Sook Kwon,Hyung Jin Kim,Shuichi Yamamoto,E K Lee,Byung Kook Lee,Jin Sook Kwon,Hyung Jin Kim,Shuichi Yamamoto,E K Lee,Byung Kook Lee,Jin Sook Kwon,Hyung Jin Kim,Shuichi Yamamoto,E K Lee,

'Solid-phase' PEGylation, in which a conjugation reaction attaches proteins to a solid matrix, has distinct advantages over the conventional, solution-phase process. We report a case study in which recombinant interferon (rhIFN) alpha-2a was adsorbed to a cation-exchange resin and PEGylated at the N-terminus by 5, 10, and 20 kDa mPEG aldehydes through reductive alkylation. After PEGylation, a salt gradient elution efficiently purified the mono-PEGylate of unwanted species such as unmodified IFN and unreacted PEG. Mono-PEGylation and purification were integrated into a single, chromatographic step. Depending on the molecular weight of the mPEG aldehyde, the mono-PEGylation yield ranged from 50 to 65%. Major problems associated with the solution-phase process such as random or uncontrollable multi-PEGylation and post-PEGylation purification difficulties were overcome. N-terminus sequencing and MALDI-TOF mass spectrophometry confirmed that the PEG molecule was conjugated only to the N-terminus. A cell proliferation study indicated reduced antiviral activity of the mono-PEGylate compared to that of the unmodified IFN. As higher molecular weight PEG was conjugated, in vitro bioactivity and antibody binding activity, as measured by a surface plasmon resonance biosensor, decreased. Nevertheless, trypsin resistance and thermal stability were considerably improved .

Solid-Phase PEGylation of Recombinant Interferon alpha-2a for Site-Specific Modification: Process Performance, Characterization, and in Vitro Bioactivity. Publishing Authors By Initials

BK Lee,JS Kwon,HJ Kim,S Yamamoto,EK Lee,BK Lee,JS Kwon,HJ Kim,S Yamamoto,EK Lee,BK Lee,JS Kwon,HJ Kim,S Yamamoto,EK Lee,

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Solid-Phase PEGylation of Recombinant Interferon alpha-2a for Site-Specific Modification: Process Performance, Characterization, and in Vitro Bioactivity. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioconjugate chemistry

VOLUME: 18

Page Numbers: 1728-34

Journal Abbreviation: Bioconjug. Chem.

ISSN: 1043-1802

DAY: 18

MONTH: 10

YEAR: 2007

Solid-Phase PEGylation of Recombinant Interferon alpha-2a for Site-Specific Modification: Process Performance, Characterization, and in Vitro Bioactivity. Information

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LANGUAGE: eng

NlmUniqueID: 9010319

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AFFILIATION: eklee@hanyang.ac.kr.

Country: United States

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MEDLINETA: Bioconjug Chem

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