Polyvalent Carbohydrate Conjugates
We have extended our investigation of the immune response to carbohydrates displayed on the exterior surface of virus capsids. We found that the immunogenicity previously detected in chickens also occurs in mice and that both IgM and IgG antibodies are produced that are highly selective for the displayed glycans. This finding is important because many pathogens and disease states are marked by the display of unusual surface glycans. If immune responses can be raised against these glycans, the possibility exists to create novel vaccines.
are of interest as cell-penetrating agents and as molecules that bind tightly to
polyanions such as DNA and RNA. The polyanion heparin is used widely to inhibit
blood clotting, but problems with heparin overdose are widespread. In the operating
room, overdoses are corrected by administering cationic molecules that complex with
heparin to reduce its effect, but the cationic molecules themselves are anticoagulants
when used at too high a concentration. We created viruslike particles with enhanced
levels of positive charge on their surfaces and found that these species efficiently
inhibit the action of heparin (Fig. 2). Furthermore, the particles are not anticoagulants
by themselves or in the presence of heparin and so appear to circumvent the major
difficulty with current antiheparin agents in clinical use. Further testing of these
particles in animal models is under way.
Bourne, C., Lee, S., Venkataiah, B., Lee, A., Korba, B., Finn, M.G., Zlotnick, A. Small-molecule effectors of hepatitis B virus capsid assembly give insight into virus life cycle. J. Virol. 82:10262, 2008.
Hong, V., Udit, A.K., Evans, R.A., Finn, M.G. Electrochemically protected copper(I)-catalyzed azide-alkyne cycloaddition. ChemBioChem 9:1481, 2008.
Kaltgrad, E., O'Reilly, M.K., Liao, L., Han, S., Paulson, J., Finn, M.G. On-virus construction of polyvalent glycan ligands for cell-surface receptor. J. Am. Chem. Soc. 130:4578, 2008.
Miermont, A., Barnhill, H., Strable, E., Lu, X., Wall, K.A., Wang, Q., Finn, M.G., Huang, X. Cowpea mosaic virus capsid, a promising carrier for the development of carbohydrate based antitumor vaccines. Chem. Eur. J. 14:4939, 2008.
Prasuhn, D.E., Jr., Singh, P., Strable, E., Brown, S., Manchester, M., Finn, M.G. Plasma clearance of bacteriophage Qβ particles as a function of surface charge. J. Am. Chem. Soc. 130:1328, 2008.
Strable, E., Prasuhn, D.E., Jr., Udit, A.K., Brown, S., Link, A.J., Ngo, J.T., Lander, G., Quispe, J., Potter, C.S., Carragher, B., Tirrell, D.A., Finn, M.G. Unnatural amino acid incorporation into virus-like particles. Bioconjug. Chem. 19:866, 2008.
Udit, A.K., Brown, S., Baksh, M.M., Finn, M.G. Immobilization of bacteriophage Qβ on metal-derivatized surfaces via polyvalent display of hexahistidine tags. J. Inorg. Biochem. 102:2142, 2008.
Udit, A.K., Everett, C., Gale, A.J., Kyle, J.R., Ozkan, M., Finn, M.G. Heparin antagonism by polyvalent display of cationic motifs on virus-like particle. ChemBioChem, in press.
Zhang, Q., Horst, R., Geralt, M., Ma, X., Hong, W.-X., Finn, M.G., Stevens, R.C., Wüthrich, K. Microscale NMR screening of new detergents for membrane protein structural biology. J. Am. Chem. Soc. 130:7357, 2008.