Methods for modulation of acetyltransferase activity and applications thereof including treatments

A method to identify modulators of histone acetyltransferase 1 activity, comprising:

• providing a substrate in a solution within a well, wherein the substrate is a peptide comprising a natural substrate of histone acetyltransferase 1, wherein the substrate is fixed to a surface of the well;
• adding to the solution a histone acetyltransferase 1, a donor molecule, and a modulator,
• wherein the donor molecule comprises a coenzyme A structure with an acetyl-like group, wherein the acetyl-like group comprises a carbonyl group and an alkyl extending from the carbonyl group, wherein the alkyl comprises a terminal alkyne,
• wherein the histone acetyltransferase 1 is extracellular and is capable of transferring the acetyl-like group of the donor molecule onto the substrate,
• wherein the modulator is a compound being assessed for its ability to modulate the transfer of the acetyl-like group onto the substrate;
• removing the histone acetyltransferase 1, the donor molecule, and the modulator from the solution, wherein the substrate remains fixed to the surface of the well;
• adding to the solution biotin-azide, wherein the azide group is configured to conjugate to the alkyne of the acetyl-like group to yield a biotin extending from the substrate via a transferred acetyl-like group;
• removing unconjugated biotin-azide from the solution, wherein the substrate remains fixed to the surface of the well;
• adding to the solution a reporter molecule conjugated with streptavidin, wherein the reporter molecule is configured to bind to the biotin extending from the substrate;
• removing unbound reporter molecule from the solution, wherein the substrate remains fixed to the surface of the well;
• and
• measuring signal of the reporter molecule bound to the substrate.