Protein side chain modification

The long-term goal of this research is to develop our photoactivatable sources of organic radicals as agents to modify proteins, either to label them (to investigate their roles in biological systems) or to modulate their activity in cells. The use of a photochemical trigger will provide spatiotemporal control of the modification event, which will be critical to its eventual use in vivo.

Our work in this area began with the effects of photogenerated methyl radical on complexes of DNA with the linker histone H1 (which was discussed on the chromatin research webpage). We have determined that methyl radicals cause the conversion of the lysine side chains (the ammonium groups) to aldehydes. The production of aldehydes is especially significant, because they are absent in naturally-occurring proteins; and therefore, they are ideal functional group "handles." In histone H1, we have been able to use these aldehydes to attach DNPH to the side chains of the proteins: