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Synthesis of Streptococcus pneumoniae Type 3 Neoglycoproteins Varying in Oligosaccharide Chain Length, Loading and Carrier Protein
Author(s) -
Lefeber Dirk J.,
Kamerling Johannis P.,
Vliegenthart Johannes F. G.
Publication year - 2001
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 - 10.1002/1521-3765(20011015)7:20<4411::aid-chem4411>3.0.co;2-t
Subject(s) - oligosaccharide , keyhole limpet hemocyanin , chemistry , conjugated system , polysaccharide , glycopeptide , stereochemistry , toxin , toxoid , biochemistry , organic chemistry , antibody , polymer , biology , immunization , antibiotics , immunology
The preparation is described of a range of neoglycoproteins containing synthesised fragments of the capsular polysaccharide of Streptococcus pneumoniae type 3, that is β ‐ D ‐Glc p A‐(1→4)‐ β ‐ D ‐Glc p ‐(1→O)‐(CH 2 ) 3 NH 2 ( 1 ), β ‐ D ‐Glc p ‐(1→3)‐ β ‐ D ‐Glc p A‐(1→4)‐ β ‐ D ‐Glc p ‐(1→O)‐(CH 2 ) 3 NH 2 ( 2 ), and β ‐ D ‐Glc p A‐(1→4)‐ β ‐ D ‐Glc p ‐(1→3)‐ β ‐ D ‐Glc p A‐(1→4)‐ β ‐ D ‐Glc p ‐(1→O)‐(CH 2 ) 3 NH 2 ( 3 ). A blockwise approach was developed for the synthesis of the protected carbohydrate chains, in which the carboxylic groups were introduced prior to deprotection by selective oxidation of HO‐6 in the presence of HO‐4 by using TEMPO (2,2,6,6‐tetramethyl‐1‐piperidinyloxy radical). After deprotection, the 3‐aminopropyl spacer of the fragments was elongated with diethyl squarate (3,4‐diethoxy‐3‐cyclobutene‐1,2‐dione) and the elongated oligosaccharides were conjugated to CRM 197 (cross‐reacting material of diphtheria toxin), KLH (keyhole limpet hemocyanin) or TT (tetanus toxoid). The resulting neoglycoconjugates varied in oligosaccharide chain length, oligosaccharide loading and protein carrier. These well‐defined conjugates are ideal probes for evaluating the influence of the different structural parameters in immunological tests.