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Endohexosaminidase‐Catalysed Glycosylation with Oxazoline Donors: Fine Tuning of Catalytic Efficiency and Reversibility
Author(s) -
Rising Thomas W. D. F.,
Heidecke Christoph D.,
Moir James W. B.,
Ling Zhenlian,
Fairbanks Antony J.
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800365
Subject(s) - oxazoline , glycosylation , chemistry , glycosyl , glycan , enzyme , stereochemistry , catalysis , mannose , hydrolysis , glycoprotein , glycosyl donor , n linked glycosylation , glycosyltransferase , biochemistry , combinatorial chemistry
A complete series of oxazoline di‐, tri‐, tetra‐, and hexasaccharides, corresponding to the core sections of N ‐linked glycoprotein high mannose glycans, together with the corresponding oligosaccharides containing a central glucose unit, were synthesised and tested as glycosyl donors for glycosylation of a GlcNAcAsn glycosyl amino acid catalysed by the endohexosaminidases M (Endo M), A (Endo A) and H (Endo H). Whilst Endo H did not catalyse any glycosylation reactions, both Endo M and Endo A efficiently catalysed glycosylations that were not limited to donors containing the Manβ(1→4)GlcNAc linkage. Precise structure activity relationships and time course studies have revealed fine‐tuning of the efficiency of the synthetic processes which correlated both with the enzyme used and the precise oxazoline structure. Efficient irreversible glycosylation was achievable with both Endo M and Endo A, further demonstrating the use of structurally modified oxazoline donors as transition state mimics in order to promote enzyme‐catalysed synthesis, whilst precluding product hydrolysis; enzymes in these cases display “glycoligase” activity.