Synthesis of Atypical Diubiquitin Chains

Post-translational modifi cation of proteins with ubiquitin (Ub) and Ub chains controls numerous biochemical events. Although it has been proven that all Ub–Ub linkages are formed in cells, studies have been limited for a long time to K48 and K63 chains as these can be generated biochemically. Access to the remaining (atypical) Ub–Ub chain types has been hampered by a lack of specifi c E2 enzymes. In this chapter we present a solution to this problem by using a native chemical ligation approach to obtain all other (i.e. K6, K11, K27, K29 and K33) diubiquitin chains.