Optimized preparation of deca(L-alanyl)-L-valinamide by 9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase synthesis on polyethylene glycol-polystyrene (PEG-PS) graft supports, with 1,8-diazobicyclo [5.4.0]-undec-7-ene (DBU) deprotection.

Abstract

Deca(L-alanyl)-L-valinamide is known to be a challenging model target for solidphase peptide synthesis, due to its hydrophobicity and its tendency to form secondary structures which inhibit acylation and deprotection. Here we report systematic studies on the synthesis of this peptide on an automated continuous-flow instrument, using the 9-fluorenylmethyloxycarbonyl (Fmoc) group for N alpha-amino protection and a polyethylene-glycol polystyrene (PEGPS) graft support. The optimal deprotection reagent proved to be DBU-piperidine-DMF (1:1:48, vol/vol/vol). The synthetic peptides were analyzed and characterized by high-performance liquid chromatography and several mass spectrometric techniques.