Heptoses
of the L-glycero-D-manno configuration are important constituents
of the lipopolysaccharide (LPS) of many Gram-negative bacteria contributing to
fundamental binding interactions of LPS with the innate and adaptive immune
system. Complementing previous synthetic approaches,1 we have set
out to synthesize di- and trisaccharide inner-core
fragments containing Hep-4-phosphates as ligands for binding and crystallographic studies with lung surfactant protein D (SP-D) as well as the
cross-protective monoclonal antibody WN1 222-5.2,3
A synthetic strategy based on early
phosphate introduction (intermediates 1
to 3) was developed. High yielding regioselective partial TIPDS
cleavage and glycosylation
reactions with glucosyl and heptosyl imidate donors allowed short synthetic
routes to the di- and trisaccharides 4
to 7 upon deprotection. These
ligands are presently being used to evaluate the binding contribution of
heptosyl phosphates when complexed to antibodies and lectins. The above concept
is currently being further developed for the assembly of larger LPS fragments.
Acknowledgments: Financial support by FWF (P 22909) is gratefully acknowledged
References: 1) K. Ekelöf, S. Oscarson. J. Carbohydr. Chem. 1995, 14, 299. 2) H. Wang, J. Head, P. Kosma, H. Brade, S.
Mueller-Loennies, S. Sheikh, B. McDonald, K. Smith, T. Ca-farella, B. Seaton,
E. Crouch. Biochem. 2008,
47, 710. 3) S. Müller-Loennies, L. Brade, R. MacKenzie, F. Di Padova, H. Brade.
J. Biol. Chem. 2003, 278, 25618.
