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Site-specific installation of methyl-lysine analogues into recombinant histones

  • US 8,278,112 B2
  • Filed: 12/20/2007
  • Issued: 10/02/2012
  • Est. Priority Date: 12/21/2006
  • Status: Active Grant
First Claim
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1. A method of introducing a site specific mono-, di, or tri-methylated lysine residue analogue into a histone H3 or H4 protein comprising the steps of:

  • (a) mutating the cysteine residues in the native sequence of the histone protein to a different amino acid residue;

    (b) mutating at least one lysine residue in the amino acid sequence of the histone protein to a cysteine residue to generate a cysteine containing protein; and

    (c) contacting the cysteine containing protein with a compound of the structure;

    R—

    CH2CH2-NH(Me)x, wherein R is a leaving group and x is 1, 2, or 3, thereby introducing a site specific mono-, di, or tri-methylated lysine residue analogue into a histone protein.

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