Methylation of geometrically constrained lysine analogues by histone lysine methyltransferases

We report synthesis and enzymatic assays on human histone lysine methyltransferase catalysed methylation of histones that possess lysine and its geometrically constrained analogues that possess rigid (E)-alkene (KE), (Z)-alkene (KZ) and alkyne (Kyne) moieties. Experimental data reveal that methyltransferases GLP and G9a do have a capacity to catalyse methylation in the order K >> KE > KZ ~ Kyne, whereas monomethyltransferase SETD8 catalyses only methylation of K and KE.