Selective PARP-1 targeting for designing chemo/radio sensitizing agents
AssigneeUniversity of Kentucky Research Foundation
InventorMarcos Oliveira
Life of this patent
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Abstract
Poly(ADP-ribose) polymerase-1 (PARP-1) is a central signaling enzyme in a cell nucleus. PARP-1 is a target for the development of radio and chemo sensitizing agents in cancer treatment as well as providing protection from stroke. An SH3 domain and an SH3 ligand domain have now been discovered on the PARP-1 protein. These domains are involved in PARP-1 activation. This discovery makes possible the use of bioinformatics tools for the design of new drugs and strategies for drug target selection, specifically targeting the PARP-1 enzyme.
Claims5
A method for identifying agents that selectively inactivate poly(ADP-ribose) polymerase-1 (PARP-1), comprising the steps of:
- (a) contacting a test compound with a polypeptide comprising the PARP-1 src-homology domain 3 (SH-3 domain), the PARP-1 SH-3 ligand domain, or both domains;
- (b) determining whether the test compound binds to the SH-3 domain or PARP-1 SH-3 ligand domain;
- (c) assaying any test compound that binds to the SH-3 domain or PARP-1 SH-3 ligand domain to determine whether the compound inactivates or prevents the activation of PARP-1;
- and
- (d) identifying the test compound as a compound that selectively inactivates or prevents the activation of PARP-1.
A method for identifying agents that activate poly(ADP-ribose) polymerase-1 (PARP-1), comprising the steps of:
- (a) contacting a test compound with a polypeptide comprising the PARP-1 src-homology domain 3 (SH-3 domain), the PARP-1 SH-3 ligand domain, or both domains;
- (b) determining whether the test compound binds to the SH-3 domain or PARP-1 SH-3 ligand domain;
- (c) assaying any test compound that binds to the SH-3 domain or PARP-1 SH-3 ligand domain to determine whether the compound activates PARP-1;
- and
- (d) identifying the test compound as a compound that selectively activates PARP-1.
Dependencies are inferred from the claim text.