Peptide inhibitors of tax-dependent transcription

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 8 to 10 amino acid residues in defined sequence

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530324, 530325, 530326, 530327, 530330, C07K 14155, C07K 402, C07K 500, C07K 700

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active

057170584

ABSTRACT:
The present invention relates to regulators of cellular gene transcription, particularly inhibitors of cellular gene transactivating factors and in particular to inhibition of gene transcription in a viral host cell that is subject to regulation by proteins or factors that originate from a virus as well as conjugates or fusion products of the inhibitors and internalization molecules, pharmaceutical compositions that can be used to alleviate or prevent the manifestation of disease states that are the result of unregulated DNA transcription as a result of transactivation, methods of treating diseases that are caused or exacerbated by the presence of transactivating factors, and regulated gene therapy to achieve long term drug delivery of the inhibitors of the present invention. This invention can be applied both to cells with genetic abnormalities or to cells infected with a virus. Preferably, at least one protein of the protein-protein interactions is a transactivating factor.

REFERENCES:
Fujsawa et al. J. of Virology 65:4525-4528 (1991).
Franklin, A.A. et al/Transactivation by the Human T-Cell Leukemia Virus Tax Protein is Mediated Through Enhanced Binding of Activating Transcription Factor-2 (ATF-2) ATF-2 Response and cAMP Element-Binding Protein (CREB)/JBC/(1993)/268(29), 21225-21231.
Paca-Uccaralertkun, S. et al/In Vitro Selection of DNA Elements Highly Responsive to the Human T-Cell Lymphotropic Virus Type I Transcriptional Activator, Tax/Mol. & Cell. Biology/(1994), 14(1), 456-462.
Wagner, S. & Green, M.R./HTLV-1 Tax Protein Stimulation of DNA Binding of bZIP Proteins by Enhancing Dimerization/Science/(1993), 262, 395-399.
Kushida, S. et al./HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis-Like Rats by Intravenous Injection of HTLV-1 Producing Rabbit or Human T-Cell Line into Adult WKA Rats/Jpn. J. Cancer Res./(1993), 84, 831-833.
Ishigura, N. et al/A Rat Model of Human T Lymphocyte Virus Type I (HTLV-I) Infection. 1. Humoral Antibody Response, Provirus Integration, and HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis-Like Myelopathy in Seronegative HTLV-I Carrier Rats/J. Exp. Med./(1992), 176, 981-989.
Feuer, G. et al/Establishment of Human T-Cell Leukemia Virus Type I T-Cell Lymphomas in Severe Combined Immunodeficient Mice/Blood/(1993), 82(3), 722-731.
Kondo, A. et al/A Model of In Vivo Cell Proliferation of Adult T-Cell Leukemia/Blood/(1993), 82(8), 2501-2509.
Unger, T. & Shaul, Y./The X Protein of the Hepatitis B Virus Acts as a Transcription Factor when Targeted to its Responsive Element/EMBO J./(1990), 9(6), 1889-1895.

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