Fig. 2. The Chemistry for a Minimal Staple in Proteins. (a) Regioselective differentiation in the formation of Dha from Cys would allow, in principle the creation of Lan from a dual Cys motif in MEK1. (b) Overall mechanistic sequence for site-selective incorporation of eliminated Dha residues (c) 1,4-Bis-alkylation/elimination agents. Synthesis: (i) SOCl2, reflux, 1.5 h then NBS, HBr/CCl4, reflux, 3 h; (ii) NH4OH, 0 °C, 1.5 h; (iii) H2O/THF (1 : 1), 0 °C, 2 h; (iv) SOCl2, reflux, 1.5 h then glycinamide then trituration in H2O.
