Method for inhibiting the formation of SET1 family core complexes
AssigneeSyracuse University
InventorsMichael S. Cosgrove, Anamika Patel
Life of this patent
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Abstract
Disclosed in this specification is a method for inhibiting the formation of SET1 family core complexes. A guanidinium-containing molecule is used to competitively inhibit the binding of the N-SET region of a SET1 protein to WDR5, thus inhibiting the formation of the SET1 family core complex. The guanidinium-containing molecule may be, for example, an arginine-containing peptide. When bound to WDR5, the guanidinium moiety is bound between the F-133 and F-263 residues of the WDR5 when a crystal structure of the bound complex is obtained.
Claims10
A method for inhibiting the histone 3 lysine 4 of (H3K4) dimethylation activity of a Suppressor of variegation Enhancer of Zeste, Trithorax (SET1) protein core complex comprising the steps of
- exposing a peptide to a cell comprising both a tryptophan-aspartic acid repeat 5 (WDR5) and a SET1 family protein, wherein the WDR5 and SET1 family protein are components of a SET1 family core complex that has histone 3 lysine 4 dimethylation (H3K4) activity when exposed to histone protein H3 , the WDR5 having a SET receptor site (N-SET) that is N-terminal to a SET domain;
- wherein the peptide has fewer than twenty residues that includes SEQ ID NO. 7 where X1 is one of S, C and A, X2 is one of A and S and X3 is one of A and E;
- and
- inhibiting the H3K4 dimethylation activity of the SET1 family core complex by allowing the peptide and the WDR5 to bind such that the peptide blocks the N-SET receptor site of WDR5 , thus inhibiting the formation of the SET1 family core complex, the inhibition being relative to an identical sample that lacks the peptide.
Dependencies are inferred from the claim text.