| The total chemical synthesis of proteins has been a longstanding goal in organic chemistry. Native chemical ligation has rendered protein total synthesis straightforward; however, for many researchers, preparation of the requisite peptide-thioester building blocks is difficult. In this thesis work, we strove to lower the barrier to protein total synthesis by developing new Boc chemistry solid phase synthesis (SPPS) methodology. This entailed: 1. development of trifluoromethanesulfonic acid as a reagent for side chain deprotection of peptide-thioesters prepared by Boc chemistry SPPS; 2. development of modified aminomethyl-polystyrene resins for use in nucleophilic cleavage of deprotected peptide-thioesters into aqueous solvents; and 3. development of a method to obtain peptide-carboxylates from peptide-thioesters, thus extending the generality of the nucleophilic cleavage strategy. Finally, biophysical studies of the snow flea antifreeze protein were carried out as a case study in the utility of protein total synthesis. |
