Synthesis of glycine-aldehydes for the C-terminus of peptides and proteins; research tool for studying ubiquitin and regulation of cell processes.
The regulation of a protein's function is a complex combination of processes that control synthesis, localization, and degradation. All of these processes must be properly regulated and are often interrelated. A key mediator of cytoplasmic and nuclear protein degradation is the protein, ubiquitin, which binds covalently to proteins in a specific domain. The ubiquitin-dependent proteolysis pathway is of vital importance in regulating normal growth and differentiation, as well as protecting against cell damage resulting from infection and mutations.
There are currently no specific substrates or selective inhibitors of the degradation enzymes associated with ubiquitin and ubiquitin-like proteins, which would allow for investigation of enzyme specificity, binding sites, affinities, and catalytic mechanisms for the enzymes of these pathways.
The current technology provides methods of synthesis for C-terminal glycine aldehydes for proteins. In particular, the method of synthesis of the C-terminal aldehyes of ubiquitin and ubiquitin-like proteins are described. Ubiquitin adledhyde is a potent inhibitor of ubiquitin C-teriminal hydrolases and ubiquitin-specific processing proteases.The availability of such inhibitors will greatly expand the ability to detect proteins modified by covalent attachment of the ubiquitin-like domain.