Kinase substrates and methods of use thereof
The invention provides kinase substrates and methods comprising their use.
1. A peptide comprising amino acid sequence WHLQTWCGS (SEQ ID NO:5) or WHLQTWCGY (SEQ ID NO:6),
or a salt thereof.
2. The peptide of claim 1 , comprising amino acid sequence WHLQTWCGS (SEQ ID NO:5).
3. The peptide of claim 1 , comprising amino acid sequence WHLQTWCGY (SEQ ID NO:6).
4. The peptide of claim 1 , further comprising the amino acid sequence of formula Ia:
W 1a -W 2a -W 3a (Ia)
and/or the amino acid sequence of formula Ib:
W 4a -W 5a -W 6a (Ib)
wherein:
the C′terminus of the amino acid sequence of formula Ia is operably linked to the N′terminus of the amino acid sequence of formula I;
the C′terminus of the amino acid sequence of formula I is operably linked to the N′terminus of the amino acid sequence of formula Ib;
W 1a is selected from the group consisting of: absent, H, K, Q, T, and V;
W 2a is selected from the group consisting of: absent, D, G, P, V, and W;
W 3a is selected form from the group consisting of: D and G;
W 4a is selected from the group consisting of: L and P;
W 5a is selected from the group consisting of: absent, H and P; and
W 6a is absent or Y;
or a salt thereof.
5. A composition comprising one or more peptides of claim 1 , a kinase, and optionally, a lanthanide metal.
6. The peptide of claim 1 , consisting of amino acid sequence WHLQTWCGS (SEQ ID NO:5), or a salt thereof.
7. The peptide of claim 1 , consisting of amino acid sequence WHLQTWCGY (SEQ ID NO:6), or a salt thereof.
8. A peptide comprising the amino acid sequence of formula I:
R 1a -R 2a -R 3a -R 4a -R 5a -R 6a -R 7a -R 8a -R 9a (I)
wherein:
the peptide is a Liver Kinase B1 (LKB1) substrate;
R 1a is W;
R 2a is selected from the group consisting of: F, H, K, and L;
R 3a is L;
R 4a is selected from the group consisting of: D, M, Q, T, and Y;
R 5a is T;
R 6a is selected from the group consisting of: C, F, S, and W;
R 7a is C;
R 8a is selected from the group consisting of: G and I; and
R 9a is selected from the group consisting of: S, T, and Y;
or a salt thereof.
9. The peptide of claim 8 , wherein:
R 1a is W;
R 2a is selected from the group consisting of: F, H, K, and L;
R 3a is L;
R 4a is Q;
R 5a is T;
R 6a is selected from the group consisting of: C, F, S, and W;
R 7a is C;
R 8a is G; and
R 9a is selected from the group consisting of: S, T, and Y;
or a salt thereof.
10. The peptide of claim 8 , wherein:
R 1a is W;
R 2a is F, K or L;
R 3a is L;
R 4a is D or Q;
R 5a is T;
R 6a is F, S or W;
R 7a is C;
R 8a is G; and
R 9a is T or S;
or a salt thereof.
11. The peptide of claim 8 , wherein R 2a is K.
12. The peptide of claim 8 , wherein R 4a is Q.
13. The peptide of claim 8 , wherein R 6a is W.
14. The peptide of claim 8 , wherein R 8a is G.
15. The peptide of claim 8 , wherein R 9a is S.
16. The peptide of claim 8 , wherein the peptide is nine amino acids in length.
17. The peptide of claim 8 , further comprising the amino acid sequence of formula Ia:
W 1a -W 2a -W 3a (Ia)
and/or the amino acid sequence of formula Ib:
W 4a -W 5a -W 6a (Ib)
wherein:
the C′terminus of the amino acid sequence of formula Ia is operably linked to the N′terminus of the amino acid sequence of formula I;
the C′terminus of the amino acid sequence of formula I is operably linked to the N′terminus of the amino acid sequence of formula Ib;
W 1a is selected from the group consisting of: absent, H, K, Q, T, and V;
W 2a is selected from the group consisting of: absent, D, G, P, V, and W;
W 3a is selected from the group consisting of: D and G;
W 4a is selected from the group consisting of: L and P;
W 5a is selected from the group consisting of: absent, H and P; and
W 6a is absent or Y;
or a salt thereof.
18. A composition comprising one or more peptides of claim 8 , a kinase, and optionally, a lanthanide metal.