Chemo-enzymatic peptide synthesis and derivatisation using Subtilisin A in anhydrous organic solvents

Abstract

In this thesis it is demonstrated that Alcalase and Cal-B in neat organic solvent can perform unique and cost-efficient conversions that are useful in the peptide area. Not only can Alcalase be used to prepare several C-terminally derivatized amino acids and peptides (such as amides, esters and arylamides), this protease is also a very efficient catalyst for peptide bond formation (optionally combined with Cal-B for ester synthesis) or even for fully enzymatic peptide synthesis strategies based on protecting group to ester interconversion. Besides stepwise peptide synthesis, Alcalase could be used to couple a large variety of (protected) peptide fragments together thereby opening new opportunities for industrial oligopeptide synthesis.