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O‐Specific Polysaccharide of Vibrio cholerae O139: Improved Synthesis and Conjugation to BSA by Squaric Acid Chemistry
Author(s) -
Lu Xiaowei,
Pfister Hélène B.,
Soliman Sameh E.,
Kováč Pavol
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800429
Subject(s) - chemistry , tetrasaccharide , linker , disaccharide , squaric acid , vibrio cholerae , bovine serum albumin , conjugated system , stereochemistry , glycopeptide , combinatorial chemistry , polysaccharide , biochemistry , organic chemistry , bacteria , polymer , antibiotics , biology , computer science , genetics , operating system
The sequence α‐Col p ‐(1→2)‐4,6‐ P ‐β‐ d ‐Gal p ‐(1→3)‐[α‐Col p ‐(1→4)]‐β‐ d ‐Glc p NAc‐(1→4)‐α‐ d ‐Gal p A‐(1→3)‐β‐ d ‐Qui p NAc constitutes the complete O‐specific polysaccharide (O‐antigen, O‐SP) of Vibrio cholerae O139. It was chemically synthesized in a linker‐equipped, conjugation‐ready form ( 7 ) and conjugated to a model protein carrier, bovine serum albumin. The preparation involved the synthesis of a tetrasaccharide intermediate sequence β‐ d ‐Gal p ‐(1→3)‐β‐ d ‐Glc p NAc‐(1→4)‐α‐ d ‐Gal p A‐(1→3)‐β‐ d ‐Qui p NAc→linker by coupling of two disaccharide intermediates followed by a stepwise, two single‐site colitosylations. The present synthesis is an alternative to the academic, small‐scale synthesis developed earlier where the final hexasaccharide assembly was achieved by simultaneous, two‐sites colitosylation. The approach reported herein comprises a few more synthetic steps but is experimentally less demanding, minimizes separation difficulties and is more convenient when tens of mgs of the final product is required. Syntheses of non‐phosphorylated and methyl ester analogues of 7 are also described.