Lysine residues, trimethylation

In the 1970s, O Leary and Samberg described the reaction of 2,4,6-trimethyl-pyrylium perchlorate 57 with a-chymotrypsin and observed the formation of a protein-pyridinium conjugate [94], Later on, the reaction of the tri-substituted pyrylium salt 58 with the proteins gelatin and a-chymotrypsin [95], glycophorin [96,97] and the Na /glucose cotransporter protein [98] was reported. In all cases, the reaction happened to exclusively involve the proteins lysine residues and formation of the corresponding pyridinium adducts were observed. 

In the last few years, we have witnessed a great surge of evidence to indicate the biochemical importance of protein methylation in cellular regulation. Trimethylation of lysine residues of protein has been shown to provide a precursor for the biosynthesis of carnitine, which is an important acyl carrier in mitochondrial membrane (4). Protein carboxymethylation is strongly implicated in leucocyte (5,6) and bacterial chemotaxis (7-10),. as well as in neu-... 

Another catalytic challenge relates to product control in cases when several methyl groups can in principle be transferred onto the same residue or atom. As mentioned, lysine methylation can lead to monomethylated, dimethylated, or trimethylated products. Because, for example, secondary amines are better nucleophiles than primary amines, it is tricky to stop a chemical alkylation reaction at the monosubstituted product. This problem... 

Some information is available on the sites of methylation in histones and cytochrome cs. Wheat germ cytochrome c contains 11 residues of lysine and two residues of c-N-trimethylysine (196). The c-N-trimethyl-... 

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