Compounds that selectively bind to expanded polyglutamine repeat domains and methods of use thereof
OwnerJames R. Burke, Warren J. Strittmatter +1inventors
InventorsJames R. Burke, Warren J. Strittmatter, Yoshitaka Nagai
Life of this patent
Estimating the term…
Abstract
Compounds that selectively bind to expanded polyglutamine repeats are disclosed. Such compounds are characterized in that they bind to a first polyglutamine peptide consisting of 60 glutamine residues under conditions in which they do not bind to a second polyglutamine peptide consisting of 20 glutamine residues. Conjugates of such compounds, nucleic acids encoding the same, and methods of use thereof are also disclosed.
Claims39
A compound according to Formula I:
- X1—R11R12R13R14—Y1 (I)
- wherein:
- R11 is Trp;
- R12 is (i) Trp or (ii) a charged amino acid selected from the group consisting of Lys, Arg and His;
- R13 is (i) Trp or (ii) a charged amino acid selected from the group consisting of Lys, Arg and His;
- subject to the proviso that one of R12 and R13 is Trp and the other is a charged amino acid;
- R14 is Trp;
- X1 is a peptide consisting of from 1 to 10 amino acids, or is deleted;
- and
- Y1 is a peptide consisting of from 1 to 10 amino acids, or is deleted;
- or a physiologically acceptable salt thereof.
A method of screening compounds for activity in treating a neurodegenerative disease characterized by the presence of expanded polyglutamine repeats, said method comprising:
- (a) providing a reagent system comprising:
- (i) a first compound comprising an expanded polyglutamine segment conjugated to a first signal group and (ii) a second compound comprising an expanded polyglutamine segment conjugated to a second signal group, wherein said first and second signal groups generate a detectable event when conjugated together, and wherein each of said expanded polyglutamine segments consists of at least 40 polyglutamine residues;
- (b) combining said test compound with said reagent system;
- and then
- (c) determining the presence or absence of said detectable event, the absence of said detectable event indicating that said test compound is a candidate for activity in treating an expanded polyglutamine repeat disease.
A method of screening compounds for activity in treating an expanded polyglutamine repeat disease, comprising:
- (a) providing a reagent system comprising an expanded polyglutamine segment conjugated to thioredoxin;
- (b) combining the test compound with the reagent system;
- and then
- (c) determining the presence or absence of aggregation in the reagent system, the absence of aggregation indicating that the compound is a candidate for activity in treating an expanded polyglutamine repeat disease.
Dependencies are inferred from the claim text.