Chemical Synthesis of K48-Linked Diubiquitin by Incorporation of a Lysine-Linked Auxiliary Handle.

We synthesized a lysine-linked auxiliary-derived building block, ϵ- N-2-mercapto-1-(2,4-dimethoxyphenyl)ethyl lysine, in 20 % isolated yield over a six-step route. The new building block is well compatible with Fmoc solid-phase peptide synthesis (SPPS) and hydrazide-based native chemical ligation (NCL). Furthermore, we successfully incorporated the new lysine-linked auxiliary handle into a protein segment and performed the chemical synthesis of K48-linked diubiquitin with stepwise NCL. [ABSTRACT FROM AUTHOR]