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Scheme 8
C-phosphonate analogues,
95
nonhydrolyzable phosphates,
96
and carba-
analogues
97
have been synthesized in a search for suciently stable
compounds that mimic the protective epitope. In the case of the carba-
analogues, the ring oxygen was replaced with a methylene group in order
to generate a carbocyclic analogue with enhancement of chemical stability.
After immunization in mice, the conjugated trimer 26 was able to induce
specific anti-MenA polysaccharide IgG antibodies with in vitro bactericidal
activity.
98
This strategy constitutes an important proof-of concept although
it is yet far from being ready for use in vaccine development.
2.5.2 MenB. In the absence of immune response to MenB CPS, the
LPS-oligosaccharide could be regarded as an alternative antigen.
99
Re-
cently, the total synthesis of a core tetrasaccharide was performed.
100
The
tetrasaccharide (27) - CRM
197
conjugate induces antibodies in mice
101
recognizing meningococcal strains across all serogroups and promoting
opsonophagocytic activity against Men B (Scheme 9).
2.5.3 MenX. The importance of serogroup X (28) was established
recently. A recent communication
102
shows the succesful preparation of
CRM197 conjugates of different Men X fragments. We also develop TT
and DT conjugates from relatively small fragments of the natural CPS.
103
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