Method for targeting degradation of intracellular proteins

Details Method for targeting degradation of intracellular proteins Method for targeting degradation of intracellular proteins

1996-02-23

1999-02-02

Patterson, Jr., Charles L.

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

424 945, 4241851, 4241921, 435 76, 435 691, 530300, A61K 3848, A61K 3851, G01N 3353, C12P 2106

Patent

active

058661212

ABSTRACT:
A method for selective targeted degradation of intracellular proteins in situ by inducing in cells a production of an agent comprising N-terminal domain as well as a C-terminal domain. The N-terminal domain destabilizes the target protein and directs its degradation when attached to it through the C-terminal domain acting as a linker between the target protein and between the protein agent of the invention. The protein degradation directing N-terminal domain is a subregion within 97 amino acids corresponding to the N-terminus of protein antizyme.

REFERENCES:
Xianqiang Li and Philip Coffino, Degradation of Ornithine Decarboxylase: Exposure of the C-Terminal Targeted by a Polyamine-Inducible Inhibitory Protein, Molecular and Cellular Biology, pp. 2377-2383, Apr. 1993.
Xianqiang Li and Philip Coffino, Regulated Degradation of Ornithine Decarboxylase Requires Interaction with the Polyamine-Inducible Protein Antizyme, Molecular and Cellular Biology, pp. 3556-3562, Aug. 1992.
Mark M. Gosink and Richard D. Vierstra, Redirecting the specificity of ubiquitination by modifying ubiquitin-conjugating enzymes, Proc. Natl. Acad. Sci. USA, Vol 92, pp 9117-9121, Sep. 1995.
Xianqiang Li and Philip Coffino, Distinct Domains of Antizyme Required for Binding and Proteolysis of Ornithine Decarboxylase, Molecular Biology, pp 87-92, Jan. 1994.
Crook et al. (1991). Cell 67 : 547-556. Nov. 1, 1991.
Glotzer et al. (1991). Nature 349 : 132-138. Jan. 10, 1991.

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