The chemistry of carbohydrates and their biology is the major emphasis of our research.
Carbohydrates play important roles in many biological processes such as inflammation,
tumor metastasis, bacterial and viral infections. Detailed understanding of many of
these processes is still lacking. Building on our strength in synthetic chemistry,
we take a multi-disciplinary approach to study this important class of molecules.
Our research encompasses several areas including synthetic organic chemistry, nanoscience and chemical immunology.
In the synthetic chemistry area, we are developing novel methodologies for assembling biologically active oligosaccharides
and glycoconjugates. Traditional carbohydrate synthesis is very tedious and time-consuming.
In order to expedite the synthetic process, we have developed novel one-pot glycosylation
methodologies, where multiple sequential glycosylation reactions are carried out in
a single reaction flask to yield desired oligosaccharides without time-consuming intermediate
purifications. One of the methods we developed, the pre-activation based iterative
one-pot method, has achieved higher synthetic efficiencies in several syntheses compared
to the automated solid phase based method. We are applying the methods we developed
to total synthesis of a wide range of highly complex oligosaccharides and glycoconjugates.
A representative example of the molecules we have synthesized is shown in Fig 1. We
are continuing to synthesize biologically important carbohydrates.
Fig 1.
In our nanoscienceprogram, we combine the multifaceted properties of carbohydrates with the unique functions
of nanoparticles by immobilizing carbohydrates onto the external surface of magnetic
nanoparticles. The magnetic glyco-nanoparticles (MGNPs) produced retain the biological
recognition of carbohydrates and at the same time enhance the avidity of carbohydrate-receptor
interactions by thousands of times. The magnetic nature of the nanoparticles enables
us to use magnetic resonance imaging (MRI) as a non-invasive method for disease detection.
An example of this is shown in Fig. 2, where the presence of atherosclerotic plaques
(the major cause of heart attack and stroke) in rabbits can be easily detected by
MRI after injection of the MGNPs. Besides detection and imaging applications, we are
exploring the utility of MGNPs for targeted drug delivery. We found that by incorporating
drugs onto MGNPs, the cytotoxicity of the drugs towards cancer cells can be significantly
enhanced. We are continuing to develop magnetic glyco-nanoparticles for non-invasive
detection and treatment of diseases such as cancer, atherosclerosis and Alzheimer’s
disease.
Fig 2.
In the immunologyarea, harnessing the awesome power of body’s immune system to fight cancer is an attractive
strategy to cancer treatment. It is well known that many tumor cells have unique carbohydrate
structures over-expressed on the cell surface. However, the low immunogenecities of
these tumor associated carbohydrate antigens present a formidable challenge for the
development of carbohydrate based anti-cancer vaccines. To overcome this obstacle,
we are developing novel carrier systems such as cowpea mosaic virus capsid (CPMV)
and bacteriophage Qβ to deliver tumor associated carbohydrate antigens to the immune
system and to boost the immune responses against carbohydrates as diagrammed in Fig.
3. We discovered that antigens displayed in a highly organized manner can elicit much
stronger immune responses. Vaccination with our constructs successfully protected
the immunized mice from tumor development in several tumor models. This is an excitingly
new direction for the development of anti-cancer vaccines.
Chemical Synthesis and Immunological Evaluation of Pe r t u ss i s - L i ke Pentasaccharide
Bearing Multiple Rare Sugars as a Potential Anti-pertussis Vaccine, Wang, P.; Huo, C.-X.; Lang, S.; Caution, K.; Nick, S. T.; Dubey, P.; Deora, R.;
Huang, X., Angew. Chem. Int. Ed. 2020, 59, 6451–6458. Highlighted in Synfacts 2020, 16, 0471.