Compounds that selectively bind to expanded polyglutamine repeat domains and methods of use thereof
AssigneeDuke University
InventorsJames R. Burke, Warren J. Strittmatter, Yoshitaka Nagai
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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.
Claims6
A method of detecting an expanded polyglutamine domain in a sample suspected of containing an expanded polyglutamine domain, said expanded polyglutamine domain consisting of at least 40 glutamine residues, said method comprising the steps of:
- (a) contacting a sample with 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 standard amino acids, or is deleted and
- Y1 is a peptide consisting of from 1 to 10 standard amino acids, or is deleted or a physiologically acceptable salt thereof,
- which compound binds to an expanded polyglutamine domain;
- and then
- (b) determining Whether the compound binds with the sample, the presence of binding indicating the presence of an expanded polyglutamine domain in said sample.
Dependencies are inferred from the claim text.