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
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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Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
Maxfield, J., & Shepherd, I. W. (1975) · Polymer · doi:10.1016/0032-3861(75)90008-7 · Cited by 236
Cited by
Saito, G., Swanson, J. A., & Lee, K.-D. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00179-5 · Cited by 1,407
Turecek, P. L., Bossard, M. J., Schoetens, F., & Ivens, I. A. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2015.11.015 · Cited by 733
PEGylation of therapeutic proteins
Jevševar, S., Kunstelj, M., & Porekar, V. G. (2010) · Biotechnology Journal · doi:10.1002/biot.200900218 · Cited by 681
Polymeric Conjugates for Drug Delivery
Larson, N., & Ghandehari, H. (2012) · Chemistry of Materials · doi:10.1021/cm2031569 · Cited by 580
Shi, D., Beasock, D., Fessler, A., Szebeni, J., Ljubimova, J. Y., Afonin, K. A., & Dobrovolskaia, M. A. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114079 · Cited by 535
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
- Publisher
- American Chemical Society (ACS)
- 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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