Day 2

Friday, March 24

From Drug Discovery to Product Development

Ligand Identification

8:25 Chairperson’s Opening Remarks

8:30 Designer Microarrays for Structural and Functional Glycomics
Dr. Ten Feizi, Professor, Director, Glycosciences Laboratory, Imperial College
We have established a state-of-the-art carbohydrate microarray technology that includes oligosaccharide probes with lipid tags, and uniquely combines the generation of oligosaccharide probes from naturally occurring sequences of glycoproteins, glycolipids, proteoglycans and polysaccharides, as well as chemically synthesized oligosaccharides. We have assembled over 200 sequence-defined oligosaccharide probes and validated their use for assigning the ligands of carbohydrate-binding receptors of the immune system. We have recently shown that, coupled with mass spectrometry, this microarray system is eminently suitable for ligand discovery for novel carbohydrate-binding proteins, by generating 'designer' microarrays from macromolecular targets. This is one of the largest, and to our knowledge the most versatile carbohydrate microarray system to date and holds promise as a novel approach to surveys of entire glycomes and proteomes for the molecular definition of carbohydrate-recognition systems.

9:00 New Methods for Glycosphingolipid Analysis and Glycosphingolipidomics
Dr. Steven B. Levery, Associate Professor, Department of Chemistry, University of New Hampshire
A significant portion of an organism's proteome consists of either enzymes for carbohydrate biosynthesis (glycosyltransferases) and degradative turnover (glycosidases), or carbohydrate binding proteins (CBPs), which function by recognizing and specifically binding to saccharide-containing ligands. Glycan arrays are important tools for making sense of the enormous complexity of CBP-ligand interactions, but their usefulness depends on the availability of reliable, detailed knowledge of the structures of glycans to be incorporated into them. Emphasizing applications to glycosphingolipids, this talk will focus on new methods being developed for characterization of glycans based on ion trap MSn techniques combined with informatics approaches, such as glycan fragment library searching and decomposition pathway constraint strategies. The use of novel glycosphingolipid derivatives that facilitate both their characterization and their incorporation into arrays as "bait" for CBPs will also be discussed.

Emerging Technologies

9:30 Emerging Technology Snapshots (sponsorships available)

10:15 Coffee Break, Poster and Exhibit Viewing

11:00 Development of Novel Bioprocesses for L-Ribose and Other Rare Sugars
Dr. Nathan Wymer, Scientist, Biocatalysis, ZuChem, Inc.
Having access to inexpensive and consistent sources of rare sugars is a significant challenge for medicinal chemists. We are currently developing a novel and scaleable bioprocess technology platform to synthesize a broad range of rare sugars at reduced costs. Our initial target for scale-up is L-ribose, a main synthetic precursor for L-nucleoside based antiviral pharmaceuticals. This presentation will then discuss our expansion of this technology to produce a broad range of rare sugars.

11:30 Natural Product Glycorandomization in Drug Discovery
Prof. Jon Thorson, Professor and Vice Chair, Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison
This presentation will cover our development of two technologies - glycorandomization (a chemoenzymatic approach, now being converted to a fermentation method) and neoglycorandomization (a chemical method) to construct libraries of natural products which solely differ by their attached carbohydrates. Recent success toward the generation of antiinfective and anticancer lead compounds will also be discussed.

12:00 Lunch on your own

Drug leads and Development

1:25 Chairperson’s Remarks
Dr. Daotian Fu, Scientific Director, Bioanalytical Development, Genzyme Corporation

2:20 Strategies for Carbohydrate Analysis Throughout Product Development
Dr. Elizabeth Higgins, President, GlycoSolutions Corporation
The field of carbohydrate analysis has evolved tremendously since the first glycoprotein therapeutics were developed. There are now more options available and it is easier to obtain more information on the glycosylation of your molecule. With all of these choices but sometimes limited resources how does a company decide how much analysis to perform and when to do it during development? And what are the risks of not doing the analysis? From working with over 40 different clients we have developed a strategy for making these types of decisions.

2:50 Refreshment Break, Poster and Exhibit Viewing

3:30 Analytical Techniques for the Characterization of Glycosaminoglycans (GAG’s)
Dr. John H. A. Amery, Sr. Scientist, Pfizer Global Biologics R&D
This presentation will illustrate a number of Glycosaminoglycans (GAG's) that are of interest to industry. This will include Hyaluronate, Heparin, and Chondroitin. There are many sources of GAG's, both biological and synthetic origin. GAG's are used for a number of purposes, and in a number of products.
There are many techniques that can be used to characterize GAG's. The following types will be presented. 
• Quantitating GAG and ionic contaminants with IC 
• Determining the disaccharide composition with HPLC 
• Determining molecular weight parameters with SEC-MALS-RID 
• Quantitating the biologic activity with a kinetic assay 

4:00 Glycoanalytics to Support Glycoprotein Drug Candidates through Development and Licensure
Dr. Joseph Siemiatkoski, Product Development, Biogen Idec
Development of therapeutic glycoproteins requires careful consideration of all aspects which may influence protein glycosylation; from the point of clone selection through development of cell culture, purification and formulation development. Supporting these various efforts requires sensitive and highly selective methods which can provide the required sample throughput. The talk will discuss the assays and approaches which we have used to support development activities as well as QC release of glycoprotein therapeutics.

4:30 Novel therapeutic leads based on recombinant mucin-type fusion proteins with tailored glycan substitution
Dr. Jan Holgersson, M.D., Ph.D., Associate Professor of Molecular Immunology, Division of Clinical Immunology, Karolinska Institute, Sweden; CSO Recopharma AB
Protein-carbohydrate interactions are essential to a number of biological processes including cell-cell and cell-microbe binding as well as antibody-mediated graft rejection. The binding of an individual protein receptor to its carbohydrate ligand is usually of low affinity, whereas the overall binding strength in the interaction between two biological entities is accomplished by multiple receptors on one surface interacting with multiple carbohydrate ligands on the other. Monovalent free oligosaccharides or glycomimetics have therefore usually low efficacy. We have developed a new class of multivalent inhibitors of protein-carbohydrate interactions based on recombinant mucin-type proteins carrying multiple O-glycans, which can be tailored to carry defined determinants by co-expression of selected glycosyltransferases.

5:00 End of Conference

For more information please contact: 
Margit Eder, Ph.D., Conference Director, Cambridge Healthtech Institute
Phone: 781-972-5478, Fax: 781-972-5425
E-mail: meder@healthtech.com

For sponsorship or exhibiting information, please contact:
Suzanne Carroll, Manager, Business Development
Phone: 781-972-5452, E-mail: scarroll@healthtech.com