There is now compelling evidence that the modification of proteins with ADP-ribose is a general feature of endogenous eucaryotice metabolism. The study of this metabolism has been limited due to a lack of analytical methods of sufficient sensitivity and selectivity. The overall objective of this proposal is to achieve an understanding of the chemistry of ADP:protein linkages. The approach is to use ADP-ribosyl amino acids as model systems. These will be synthesized, isolated and characterized and used as references standards for the development of methods which will allow the direct identification of ADP-ribosyl amino acid residues in endogenous proteins. The research will lay the groundwork for understanding endogenous eucaryotic ADP-ribose metabolism and the mode of action of bacterial toxins.
