Sox-based kinase sensor
Peptidyl sensors comprise a metal-binding peptide and one or two kinase recognition sequences with a hydroxyamino acid that can be phosphorylated in the presence of a kinase.
1. A compound of structure (I):
wherein R 1 is hydroxy, amino, or thiol;
R 2 and R 3 are each independently hydrogen, an electron-withdrawing group, or —SO 2 X;
each R 4 is independently hydrogen, an electron-withdrawing group or —SO 2 X, wherein R 4 can substitute any open valence of any ring within structure (I);
X is —OR′ or —NR′R″;
Y is halogen, —SH, —NR′R′″, —CHO, or —CO 2 H;
R′ and R″ are each independently hydrogen or C 1-6 alkyl;
R′″ is hydrogen, unsubstituted C 1-6 alkyl, tBoc or Fmoc;
n is 0, 1, 2 or 3; and
m is 1, 2, or 3, and
wherein at least one of R 2 , R 3 or R 4 is —SO 2 X and at least another one of R 2 , R 3 or R 4 is an electron-withdrawing group.
2. The compound of claim 1 , which has the structure:
wherein R 1 is hydroxy, amino, or thiol;
R 2 and R 3 are each independently hydrogen, an electron-withdrawing group, or —SO 2 X;
each R 4 is independently hydrogen, an electron-withdrawing group or —SO 2 X, wherein R 4 can substitute any open valence of any ring within the structure;
X is —OR′ or —NR′R″;
Y is halogen, —SH, —NR′R′″, —CHO, or —CO 2 H;
R′ and R″ are each independently hydrogen or C 1-6 alkyl;
R′″ is hydrogen, unsubstituted C 1-6 alkyl, tBoc or Fmoc;
n is 0, 1, 2 or 3; and
m is 1 or 2, and
wherein at least one of R 2 , R 3 or R 4 is an electron-withdrawing group.
3. The compound of claim 1 , which has the structure:
wherein R 2 and R 3 are each independently hydrogen, an electron-withdrawing group, or —SO 2 X;
each R 4 is independently hydrogen, an electron-withdrawing group or —SO 2 X, wherein R 4 can substitute any open valence of any ring within the structure;
X is —OR′ or —NR′R″;
Y is halogen, —SH, —NR′R′″, —CHO, or —CO 2 H;
R′ and R″ are each independently hydrogen or C 1-6 alkyl;
R′″ is hydrogen, unsubstituted C 1-6 alkyl, tBoc or Fmoc;
n is 0, 1, 2 or 3; and
m is 1, 2 or 3, and
wherein at least one of R 2 , R 3 or R 4 is —SO 2 X and at least another one of R 2 , R 3 or R 4 is an electron-withdrawing group.
4. The compound of claim 1 , which has the structure:
wherein R 2 and R 3 are each independently hydrogen, an electron-withdrawing group, or —SO 2 X;
each R 4 is independently hydrogen, an electron-withdrawing group or —SO 2 X, wherein R 4 can substitute any open valence of any ring within the structure;
X is —OR′ or —NR′R″;
Y is halogen, —SH, —NR′R′″, —CHO, or —CO 2 H;
R′ and R″ are each independently hydrogen or C 1-6 alkyl;
R′″ is hydrogen, unsubstituted C 1-6 alkyl, tBoc or Fmoc;
n is 0, 1, 2 or 3; and
m is 1 or 2, and
wherein at least one of R 2 , R 3 or R 4 is an electron-withdrawing group.
5. A peptide comprising an amino acid residue, the side chain of the amino acid residue modified with a compound of structure (I):
wherein R 1 is hydroxy, amino, or thiol;
R 2 and R 3 are each independently hydrogen, an electron-withdrawing group, or —SO 2 X;
each R 4 is independently hydrogen, an electron-withdrawing group or —SO 2 X, wherein R 4 can substitute any open valence of any ring within structure (I);
X is —OR′ or —NR′R″;
Y is halogen, —SH, —NR′R′″, —CHO, or —CO 2 H;
R′ and R″ are each independently hydrogen or C 1-6 alkyl;
R′″ is hydrogen, C 1-6 alkyl, tBoc or Fmoc;
n is 0, 1, 2 or 3; and
m is 1, 2 or 3, 4, and
wherein at least one of R 2 , R 3 or R 4 is —SO 2 X and at least another one of R 2 , R 3 or R 4 is an electron-withdrawing group.
6. The peptide of claim 5 , wherein the peptide further comprises a kinase recognition sequence.
7. The peptide of claim 5 , wherein the peptide further comprises two kinase recognition sequences.
8. The compound of claim 1 , which has the structure:
wherein R 1 is hydroxy, amino, or thiol;
R 2 and R 3 are each hydrogen;
each R 4 is independently hydrogen, an electron-withdrawing group or —SO 2 X, wherein R 4 can substitute any open valence of any ring within the structure;
X is —OR′ or —NR′R″;
Y is halogen, —SH, —NR′R′″, —CHO, or —CO 2 H;
R′ and R″ are each independently hydrogen or C 1-6 alkyl;
R′″ is hydrogen, unsubstituted C 1-6 alkyl, tBoc or Fmoc;
n is 0, 1, 2 or 3; and
m is 1 or 2, and
wherein at least one R 4 is an electron-withdrawing group.
9. The compound of claim 1 , which has the structure:
wherein R 2 and R 3 are each hydrogen;
each R 4 is independently hydrogen, an electron-withdrawing group or —SO 2 X, wherein R 4 can substitute any open valence of any ring within the structure;
X is —OR′ or —NR′R″;
Y is halogen, —SH, —NR′R′″, —CHO, or —CO 2 H;
R′ and R″ are each independently hydrogen or C 1-6 alkyl;
R′″ is hydrogen, unsubstituted C 1-6 alkyl, tBoc or Fmoc;
n is 0, 1, 2 or 3; and
m is 1, 2 or 3, and
wherein at least one R 4 is —SO 2 X and at least another one of R 4 is an electron-withdrawing group.
10. The compound of claim 1 , which has the structure:
wherein R 2 and R 3 are each hydrogen;
each R 4 is independently hydrogen, an electron-withdrawing group or —SO 2 X, wherein R 4 can substitute any open valence of any ring within the structure;
X is —OR′ or —NR′R″;
Y is halogen, —SH, —NR′R′″, —CHO, or —CO 2 H;
R′ and R″ are each independently hydrogen or C 1-6 alkyl;
R′″ is hydrogen, unsubstituted C 1-6 alkyl, tBoc or Fmoc;
n is 0, 1, 2 or 3; and
m is 1 or 2, and
wherein at least one R 4 is an electron-withdrawing group.