Title of Talk

Carbohydrate globules: hexaphenylbenzene-cored ‘snowflake’ dendrimers for presentation of Poly-N-acetylglucosamine (PNAG) polysaccharides.

 

Abstract

The development of synthetic vaccines displaying carbohydrate antigens has been hampered by the complexity, size and difficulty of synthesis of the antigens.  We have developed a series of rigid antigen presenting scaffolds (RAPS) designed to allow presentation of components of antigens in a predictable and reproducible relative configuration.  The scaffolds also allow for the display of simplified saccharide units in a way that approximates the surface topology of the complete complex carbohydrate antigen.

Poly-N-acetylglucosamine (PNAG) saccharides are an important constituent of bacterial biofilms, such as those produced by Staphylococcus aureus.  The native polysaccharide is a polymer of up to 130 units of β-(1à6)-glucosamine.  In order to facilitate the development of fully synthetic vaccine constructs bearing shorter oligosaccharides we have developed a simple two-step iterative method for the synthesis of β-(1à6)-glucosamine oligosaccharides that are structurally similar to PNAG.1  We illustrate the method with the formation of the di, tri, tetra and pentasaccharide analogues.  Twelve copies of these oligosaccharides have been efficiently coupled with the acetylenyl surface groups of the G1-hexaphenyl bezene cored ‘snowflake’-shaped dendrimer via a Huisgen 1,3-dipolar cycloaddition reaction to give a series of multivalent carbohydrate constructs that mimic the globular nodules of polysaccharide intercellular adhesin (PIA) produced by Staphylococcus aureus.2Details of the syntheses of these molecules will be presented.

 

Figure 1. Iterative synthesis of PNAG oligosaccharides

 

References:

1. Weaver, Lucy G.; Singh, Yogendra; Blanchfield, Joanne T.; Burn, Paul L. Carbohydrate Research, 2013, 371, 68 

2. Weaver, Lucy G.; Singh, Yogendra; Vamvounis, George; Wyatt, Mark F.; Burn, Paul L.; Blanchfield, Joanne T. Polymer Chemistry submitted

Joanne Blanchfield, Dr, Senior Lecturer

 

School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, QLD 4072, AUSTRALIA

e-mail: j.blanchfield@uq.edu.au


Profile. I completed my BSc and PhD at the University of Queensland.  I then conducted Postdoctoral research at Johns Hopkins University, Australian National University and in the Pharmacy School at UQ before being appointed to the academic staff of the School of Chemistry and Molecular Biosciences in 2003.  My research broadly concerns drug and vaccine development and delivery. Our group has projects involving the design synthesis of antigen presenting constructs designed to mimic more complex antigen structures using simplified components on a rigid scaffold.  We are currently studying the construction of antigens from Staphylococcus aureus, HIV and HPV.  My group also investigates the development of new peptide based CNS active drugs and the delivery of these across the blood brain barrier and we have projects concerning the isolation and examination of the bioactive compounds from herbal extracts.  I have authored over 30 papers and my research been the subject of two US patents.

 

Selected Publications

1. Weaver, Lucy G.; Singh, Yogendra; Blanchfield, Joanne T.; Burn, Paul L. Carbohydrate Research, 2013, 371, 68

2. Weaver, Lucy G.; Singh, Yogendra; Vamvounis, George; Wyatt, Mark F.; Burn, Paul L.; Blanchfield, Joanne T. Polymer Chemistry submitted

3. Varamini, P.; Mansfeld, F.M.; Blanchfield, J.T.; Wyse, B.D.; Smith, .T.; Toth, I PLoS One, 2012, 7, e41909

4. Varamini, P.; Mansfeld, F.M.; Blanchfield, J.T.; Wyse, B.D.; Smith, .T.; Toth, I. J. Med. Chem. 2012, 55, 5859

5. Cros, C.D.; Toth, I.; Blanchfield, J.T. Bioorg. Med. Chem.2011, 19, 1528