Enzyme-labile protecting groups in peptide synthesis: development of glucose- and galactose-derived urethanes.
The development of the tetra-O-acetyl-D-glucopyranosyloxycarbonyl (AGlOC) and tetra-O-acetyl-beta-D-galactopyranosyloxycarbonyl (AGalOC) protecting groups, which are fully enzyme-labile, carbohydrate-derived urethanes, is described. The protected amino acids were easily synthesized and subsequently converted into a series of model dipeptides through classical peptide couplings. Cleavage of an alpha/beta-anomeric mixture of a model AGlOC dipeptide was achieved with a "one-pot" procedure in good yield. To gain a better understanding of the enzymatic deprotection reaction, the AGalOC group was removed through a two step biotransformation (lipase catalyzed deacetylation, followed by beta-galactosidase catalyzed glycosidic bond fragmentation). Under these very mild reaction conditions (aq. buffer pH7.0, 37 degrees C), the desired N-terminal, unprotected dipeptide conjugates were obtained. The methodology was further utilized for the synthesis of an advanced tetrapeptide model system.
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Universität Karlsruhe, Institut für Organische Chemie, Germany.
Kappes-Roth
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Waldmann
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D000107:Acetylation; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D005697:Galactosides / Q000737:chemistry / Q000378:metabolism*; D005960:Glucosides / Q000737:chemistry / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D014520:Urethane / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
D000596:Amino Acids; D005697:Galactosides; D005960:Glucosides; D010455:Peptides; D014520:Urethane; D008049:Lipase; D006026:Glycoside Hydrolases