Fast conventional Fmoc solid-phase peptide synthesis: a comparative study of different activators.

The ability to speed up conventional Fmoc solid-phase peptide synthesis (SPPS) has many advantages including increased productivity. One way to speed up conventional Fmoc SPPS is the choice of activator. Recently, several new activators have been introduced into the market, and they were evaluated along with some older activators for their ability to synthesize a range of peptides with shorter and longer reaction times. It was found that HDMC, PyClock, COMU, HCTU, and HATU worked well at shorter reaction times (2 × 1 min), but PyOxim and TFFH only worked well at longer reaction times. The performance of PyBOP at shorter reaction times was poor only for more difficult sequences. These results are important for selecting an appropriate activator for fast SPPS applications.