Electrostatic Assistance of 4-Mercaptophenylacetic acid catalyzed Native Chemical Ligation


4-mercaptophenylacetic acid (MPAA) is a popular catalyst of the native chemical ligation (NCL) but has to be used in large excess for achieving practically useful rates (up to 50-100 equivalents). We report here that the catalytic potency of MPAA can be boosted by introducing a stretch of arginines in the departing thiol from the thioester. By doing so, the electrostatically-assisted NCL reaction proceeded rapidly by using sub-stoichiometric concentrations of MPAA, an advantage that enabled useful synthetic applications.


Supplementary material

Supplementary Information
Detailed protocols and characterization data for all compounds