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J. Biol. Chem., Vol. 277, Issue 5, 3440-3446, February 1, 2002
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From the Synthetic oligomers of the antigenic
Candida albicans (1
The Unique Solution Structure and Immunochemistry of the
Candida albicans
-1,2-Mannopyranan Cell Wall
Antigens*,
,,,
Department of Chemistry, the University of
Alberta, Edmonton, Alberta T6G 2G2, Canada and the
§ Department of Microbiology, Montana State University,
Bozeman, Montana 59717-3520
2)-
-mannopyranans adopt a compact
solution conformation that leads to numerous inter-residue nuclear
Overhauser effects, including unprecedented nuclear Overhauser effects
between n and n + 3 residues. In excellent
agreement with experimentally determined distances, unrestrained
molecular dynamics point to a single family of conformations that
approximate a compact helical motif with a three-residue repeat for
this unique homopolymer. When the synthetic di- to hexasaccharides
were employed as inhibitors of monoclonal antibodies, which protect
mice against a lethal dose of the yeast pathogen, a novel pattern of
inhibitor activity was observed. Instead of the paradigm first reported
by Kabat (Kabat, E. A. (1962) Fed. Proc. 21, 694-701;
Kabat, E. A. (1966) J. Immunol. 97, 1-11), wherein homo-oligosaccharides exhibit increasing inhibitory activity with increasing size, here the maximum activity is reached for di- and
trisaccharides and diminishes significantly for tetra-, penta-, and
hexasaccharides. These immunochemical data correlate with the ordered
conformation of the -1,2-linked mannopyranan and imply that a
uniquely small antigenic determinant has potential as a component of
synthetic conjugate vaccines against Candida albicans.
*
This work was supported in part by research grants from the
National Science and Engineering Research Council of Canada (to D. R. B.), the University of Alberta, and National Science and Engineering Research Council of Canada postgraduate studentship awards
(to M. N.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The on-line version of this article (available at
http://www.jbc.org) contains Tables I-III and Figs.
1-5.
¶
Supported by National Institutes of Health Research
Grants RO1 AI24912, RO1 DE13982, and PO1 AI37194.
To whom correspondence should be addressed: Dept. of
Chemistry, the University of Alberta, Edmonton, Alberta T6G 2G2,
Canada. Tel.: 780-492-8808; Fax: 780-492-7705; E-mail:
Dave.Bundle@ualberta.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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