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Cited by 611

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Rational Design of a Potent, Long-Lasting Form of Interferon: A 40 kDa Branched Polyethylene Glycol-Conjugated Interferon α-2a for the Treatment of Hepatitis C

Bailon, Pascal, Palleroni, Alicia, Schaffer, Carol A., Spence, Cheryl L., Fung, Wen-Jian, Porter, Jill E., Ehrlich, George K., Pan, Wen, Xu, Zhi-Xin, Modi, Marlene W., Farid, Adrienne, Berthold, Wolfgang, Graves, Mary·2001·Bioconjugate Chemistry

Abstract

A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40 kilodalton branched poly(ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon alpha-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon alpha-2a was found to be only 7% of the original activity. In contrast, the in vivo antitumor activity was severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha-2a showed no immunogenicity in mice. After subcutaneous injection of pegylated interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase in mean plasma residence time concomitant with sustained serum concentrations were observed relative to interferon alpha-2a. These preclinical results suggest a significantly enhanced human pharmacological profile for pegylated interferon alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed the superior efficacy of pegylated interferon alpha-2a compared to unmodified interferon alpha-2a.

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Crossref · 10.1021/bc000082g

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Metadata

Authors
Bailon, P., Palleroni, A., Schaffer, C. A., Spence, C. L., Fung, W.-J., Porter, J. E., Ehrlich, G. K., Pan, W., Xu, Z.-X., Modi, M. W., Farid, A., Berthold, W., & Graves, M.
Venue
Bioconjugate Chemistry
Published
2001-02-16
Volume
12
Issue
2
Pages
195-202
ISSN
  • 1043-1802 (ISSN-L)
  • 1520-4812
OpenAlex
W1987119060
Cited by
611
References
2
FWCI
13.91
Type
journal article
Language
en
Open access
closed

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