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Existing and future therapeutic options for hepatitis C virus infection.

100%
Bretner M.
|
2005
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vol. 52
|
issue 1
57-70
EN
Hepatitis C virus (HCV) infection is an important cause of chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver failure worldwide. Chronic hepatitis C virus infection is treated with interferon-a (IFN-α), pegylated interferon-α (PEG-IFNα) alone or in combination with ribavirin; however, a significant fraction of patients either fail to respond or relapse after cessation of therapy. Efforts to identify and develop highly specific and potent HCV inhibitors have intensified recently. Each of the virally encoded replication enzymes has been a focus of studies as well as viral receptors and the host immune system. This review summarizes recent progress in the search for novel anti-HCV agents.
2
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Different properties of four molecular forms of protein kinase CK2 from Saccharomyces cerevisiae

39%
Domańska K., Zieliński R., Kubiński K., Sajnaga E., Masłyk M., Bretner M., Szyszka R.
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2005
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vol. 52
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issue 4
947-951
EN
CK2 is a pleiotropic constitutively active serine/threonine protein kinase composed of two catalytic α- and two regulatory β-subunits, whose regulation is still not well understood. It seems to play an essential role in regulation of many cellular processes. Four active forms of CK2, composed of αα'ββ', α2ββ', α'2ββ', and a free α'-subunit were isolated from wild-type yeast and strains containing a single deletion of the catalytic subunit. Each species exhibits properties typical for CK2, but they differ in substrate specificity and sensitivity to inhibitors. This suggests that each CK2 isomer may regulate different process or may differ in the way of its regulation.
3
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NTPase/helicase of Flaviviridae: inhibitors and inhibition of the enzyme.

39%
Borowski P., Niebuhr A., Schmitz H., Hosmane R. S., Bretner M., Siwecka M. A., Kulikowski T.
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2002
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vol. 49
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issue 3
597-614
EN
RNA nucleoside triphosphatases (NTPase)/helicases represent a large family of proteins that are ubiquitously distributed over a wide range of organisms. The enzymes play essential role in cell development and differentiation, and some of them are involved in transcription and replication of viral single-stranded RNA genomes. The enzymatic activities of a NTPase/helicase were also detected in the carboxyl-terminal non-structural protein 3 (NS3) of members of the Flaviviridae family. The crucial role of the enzyme for the virus life cycle was demonstrated in knock out experiments and by using NTPase/helicase specific inhibitors. This makes the enzyme an attractive target for development of Flaviviridae-specific antiviral therapies. This review will summarize our knowledge about the function and structure of the enzyme, update the spectrum of inhibitors of the enzymatic activities of the NTPase/helicase and describe the different mechanisms by which the compounds act. Some of the compounds reviewed herein could show potential utility as antiviral agents against Flaviviridae viruses.
4
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Acyclic analogues of 5-fluoro-dUMP and 5-fluoro-2'-deoxyuridine: Synthesis and inhibition of thymidylate synthase and tumour cell growth

39%
Felczak K., Gołos B., Dzik J. M., Rode W., Bretner M., Shugar D., Kulikowski T.
Acta Biochimica Polonica
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1998
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vol. 45
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issue 1
75-82
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