Photoreactive synthetic regulator of protein function and methods of use thereof
AssigneeThe Regents of the University of California
InventorsDirk Trauner, Ehud Y. Isacoff, Richard H. Kramer, Matthew R. Banghart, Doris L. Fortin, Alexandre Mourot
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Abstract
The present disclosure provides a photoreactive synthetic regulator of protein function. The present disclosure further provides a light-regulated polypeptide that includes a subject synthetic regulator. Also provided are cells and membranes comprising a subject light-regulated polypeptide. The present disclosure further provides methods of modulating protein function, involving use of light.
Claims30
A method for conferring light sensitivity to a cell in an eye of a subject, the method comprising administering to an eye of the subject an effective amount of a compound having the formula:
- (A)n-X1-(B)m-X2-(C)p
- wherein
- A is a polypeptide association moiety selected from hydrogen, C1-C10 alkyl, substituted C1-C10 alkyl, —NR10R11, —NR12C(O)R13, C2-10 alkenyl, substituted C2-10 alkenyl, C2-10 alkynyl, substituted C2-10 alkynyl, C6-20 aryl, substituted C6-20 aryl, heteroaryl, heterocyclic, heterocyclooxy, heterocyclothio, heteroarylamino, heterocycloamino, C4-10 cycloalkyl, substituted C4-10 cycloalkyl, C4-10 cycloalkenyl, substituted C4-10 cycloalkenyl, cyano, halo, —OR10, —C(O)OR10, —SR10, —S(O)R10, —S(O)2R10;
- wherein
- R10 and R11 are independently selected from hydrogen, C1-10 alkyl, and substituted C1-C10 alkyl;
- R12 is hydrogen or C1-10 alkyl;
- and
- R13 is selected from hydrogen, C1-10 alkyl, C1-8 alkenyl, C6-10 aryl, and substituted C1-10 alkyl;
- B is a photoisomerizable group comprising an azobenzene;
- C is a ligand selected from an agonist, an antagonist, an allosteric modulator, and a blocker;
- n is 1;
- each of m and p is independently an integer from 1 to 10;
- and
- X1 and X2 are each an optional spacer independently selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, and aminoacyl,
- or a pharmaceutically acceptable salt thereof,
- wherein the administering is sufficient to confer light sensitivity to the cell in the eye of the subject.
Dependencies are inferred from the claim text.