The stepwise chemical approach on polymeric supports is practically limited to polypeptides with typically < 50 amino acid residues due to the accumulation of side products and partial epimerization that complicate product purification and decrease yields. The synthesis of larger proteins requires blockwise enzymatic coupling of synthetic fragments. An ingenious combination of chemical and enzymatic strategies has been demonstrated in a new synthesis of RNase A using the subtilisin mutant subtiligase[16] and, furthermore, the application of an irreversible C-N ligation strategy based on the substrate mimetic concept should promote the progress in the practical synthesis of peptides and proteins as pharmaceuticals in the near future. In addition to enzyme-supported C-N ligations, enzyme-catalyzed deblocking reactions [23] using a broad range of proteases have proven their efficiency in the construction of complex peptide conjugates [24]. http://www.sigmaaldrich.com/Brands/Fluka___Riedel_Home/Organic___Synthetic/Peptide_Synthesis/Enzymat...
"If the facts don't fit the theory, change the facts."