Kinesin motor modulators derived from the marine sponge Adocia
AssigneeThe Regents of the University of California
InventorsLawrence S. B. Goldstein, David John Faulkner, Roman Sakowicz, Michael S. Berdelis, Christine L. Blackburn, Cordula Hopmann
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Abstract
This invention provides novel compounds derived from a marine sponge, Adocia sp., that specifically modulat kinesin activity by targeting the kinesin motor domain and mimicking the activity a microtubule. The compounds act as potent anti-mitogens are useful in a wide variety of in vitro and in vivo applications.
Claims17
A method of identifying a compound that specifically modulates a kinesin motor at a microtubule binding site, said method comprising the steps of:
- (i) assaying for competitive inhibition of said motor by said compound at a kinesin ATPase site;
- (ii) assaying for competitive inhibition of said motor by said compound at a microtubule binding site;
- (iii) identifying a small compound as a kinesin modulator specific to a microtubule binding site when said small compound is a competitive modulator at said microtubule binding site, but not at said ATPase site.
A method of modulating kinesin motor activity, said method comprising contacting said kinesin motor with a small organic molecule that competitively inhibits said kinesin motor at a microtubule binding site.
A method of identifying an agent that modulates the kinesin inhibitory activity of an Adocia kinesin inhibitor, said method comprising:
- (i) contacting a microtubule, a kinesin motor, and an Adocia kinesin inhibitor with a candidate agent;
- and
- (ii) detecting a change in the kinesin inhibitory activity of the Adocia kinesin inhibitor resulting from said contacting, wherein a change indicates the identification of an agent that modulates the kinesin inhibitory activity of the Adocia kinesin inhibitor.
A method of identifying an agent that interferes with the binding of an Adocia kinesin inhibitor with a kinesin, said method comprising:
- (i) contacting a kinesin and an Adocia kinesin inhibitor with a candidate agent;
- and
- (ii) detecting a decrease in the binding of the Adocia kinesin inhibitor with the kinesin resulting from said contacting, wherein a decrease indicates the identification of an agent that interferes with the binding of the Adocia kinesin inhibitor and the kinesin.
A complex comprising an Adocia kinesin inhibitor and a kinesin.
Dependencies are inferred from the claim text.