Enzymatic Synthesis of Peptides and Ras Lipopeptides Employing Choline Ester as a Solubilizing, Protecting, and Activating Group

摘要

For the synthesis of peptides and sensitive complex peptide conjugates, enzymatic transformations offer advantageous alternatives to classical chemical methods. Thus, for instance, biocataiyzed deblocking reactions have proven their efficiency in theconstruction of glyco- and lipopeptides, and protease-mediated peptide synthesis in ice can be used to couple amino acids and peptides without racemization. However, enzymatic reactions often are hampered or even prevented by the low solubility of the protected peptides in aqueous reaction media, resulting in limited accessibility of the substrates to the biocataiysts. This difficulty can be overcome by employing solubilizing blocking groups. Their removal, however, often requires reaction conditions that cannot be tolerated in the construction of sensitive peptide conjugates. We now report that choiine esters are advantageous solubility-enhancing protecting groups for the synthesis of peptides and lipopeptides under extremely mild conditions.