Glycosylation: Opportunities in Drug Development

 Copenhagen, June 11-14, 2007

Organizing committee:

Ole Hindsgaul (Copenhagen), Henrik Clausen (Copenhagen), 
Monica M. Palcic (Copenhagen) and Povl Krogsgaard-Larsen (Copenhagen)

Invited speakers and chairmen:
BERTOZZI, CAROLYN R. (US) - BOCK, KLAUS (DK) - BOREN, THOMAS (SE) - BURCHELL, JOY (UK) - CROCKER, PAUL (UK) - DAVIS, BEN (UK) - DENNIS, JIM (CA) - DESNICK, ROBERT J. (US) - ENDO, TAMAO (JP) - ERNST, BEAT (CH) - FREEZE, HUDSON (US) - GERNGROSS, TILLMAN U. (US) - HARRIS, REED J. (US) - HART, GERALD W. (US) - HENRISSAT, BERNARD (FR) - HOFFMEISTER, KARIN M. (US) - HOLMDAHL, RIKARD (SE) - JENSENIUS, JENS C. (DK) - LEFFLER, HAKON (SE) - LINDAHL, ULF (SE) - LIVINGSTON, PHILIP O. (US) - MARTH, JAMEY D. (US) - MIYAKE, KENSUKE (JP) - PAULSON, JIM (US) - PETERS, THOMAS (DE) - PIERCE, MICHAEL (US) - RAETZ, CHRISTIAN R. H. (US) - SAMAIN, ERIC (FR) - SCHNAAR, RONALD L. (US) - SEEBERGER, PETER H. (CH) - STANLEY, PAMELA (US) - THORSON, JON S. (US) - VAN BOECKEL, STAN (NL) - VEREZ-BENCOMO, VICENTE (CU) - VON ITZSTEIN, MARK (AU) - ZOPF, DAVID (US)

Synopsis:

Many carbohydrates in themselves, such as aminoglycoside antibiotics, have long been used as drugs. Other antibiotics like erythromycin and the “drug-of-last-resort” Vancomycin, as well as important cardiovascular drugs and anti-cancer agents, require correct glycosylation for their activity. Yet the glycosylation-drug connection has remained largely unappreciated and unexploited, due in large part to the inherent complexity of the field of Glycobiology and the great difficulties in both producing and analyzing complex carbohydrate-containing structures.

This situation is now changing rapidly. Recombinant glycoprotein hormones and antibodies have become multi-billion dollar drugs, and isolated heterogeneous anticoagulants such as heparins are giving way to chemically well-defined synthetic analogs. Glycosylation of both proteins and small molecules is therefore being reassessed with respect to pharmaceutical potential.

Breakthroughs in chemical and enzymatic synthesis have appeared, permitting systematic research on well-defined glycosylated molecules, including carbohydrate-base vaccines. Enormous progress has been made in areas spanning the controlled expression of glycosylated proteins to the discovery of new carbohydrate-dependent pathogensis: examples include the binding of viruses, toxins and bacteria to cells. Finally, the maturation of the field of Glycobiology has suggested unanticipated targets for carbohydrate-based inhibition, including cell-cell adhesion and signalling.

Benzon Symposium No. 54 hass examined the state-of-the-art and explored future possibilities in the glycosylation-drug arena with the widest possible scope: from small molecules through to cells and animals.

For selected photos click here:

Scientific Programme:

Ole HINDSGAUL: Welcome and Opening Comments

Opening Lecture

Chair: Ole Hindsgaul

James C. Paulson: Functional Glycomics

Session I: Glycosylation and Drugs

Chair: Ole Hindsgaul

Mark von Itzstein: Targeting Carbohydrate-Recognizing Proteins as Drug Discovery Targets

Stan van Boeckel: Synthetic Heparin: From Fondaparinux and Idraparinux to a Novel Carbocarrier Technology for Therapeutic Proteins

Vicente Verez-Bencomo: Development of Haemophilus Influenzae Type b Conjugate Vaccines Using a Synthetic Antigen

Oral presentation selected from submitted abstracts:

Stefan Oscarson: Approaches Towards Glycoconjugate Vaccines Against Neisseria Meningitidis Based on Synthetic Oligosaccharide Structures

Session II: New Targets for Carbohydrate-Based Drugs

Chair: Klaus Bock

Christian R.H. Raetz: Structure and Inhibition of Enzymes that Assemble Gram-Negative Endotoxin, a Potent Saccharolipid Activator of Innate Immunity

Beat Ernst: From Carbohydrate Leads to Drugs: Why is it so Difficult?

Hakon Leffler: Galectins as Drug Targets in Cancer and Inflammation

Thomas Borén: Helicobacter Pylori Adhesins and Glycan Receptors

Oral presentations selected from submitted abstracts:

Knud J. Jensen: Solid-Phase Chemical Tools for Glycomics: Glycochips and Nanoparticles

Shin-Ichiro Nishimura: Glycoblotting-Based Clinical Glycomics

Posters: Small Molecules and New Tools

Authors present posters Nos. I-1 – I-35.

Session III:  Protein Glycosylation

Chair: Michael Pierce

Gerald W. Hart: O-GlcNAc Cycling on Regulatory Proteins: A Nutrient/Stress Sensor Regulating Transcription, Translation, and Signalling

Pamela Stanley: Roles for O-Fucose Glycans in Notch Signalling

Reed J. Harris: Glycosylation in Biopharmaceuticals

David Zopf: Modifying Glycans to Improve Performance of Glycoprotein Therapeutics

Ulf Lindahl: Heparan Sulphate-Protein Interactions: Are They Specific?

Session IV: New Tools - I

Chair: Monica Palcic

Carolyn R. Bertozzi: Shedding Light on Glycans

Tillman U. Gerngross: The Use of Humanized Yeast to Explore the Glyco-Design Space – A Novel Discovery and Manufacturing Platform for Biotherapeutics

Eric Samain: Synthesis of Complex Oligosaccharides Using Metabolically Engineered Bacteria

Ben Davis: Sugar & Enzymes: Exploring and Exploiting Protein-Carbohydrate Interactions

Bernard Henrissat: Carbohydrate Active Enzymes

Oral presentation selected from submitted abstracts:

Steffen Goletz: A Novel Human Cellular Toolbox for Expression of Glyco-Optimised Fully Human Glycoprotein

Posters: Glycoconjugates and Glycoenzymes

Authors present posters Nos. II-1 – II-34.

Session V: New Tools - II

Chair: Beat Ernst

Peter H. Seeberger: Automated Oligosaccharide Synthesis

Jon S. Thorson: Challenges and Opportunities in Natural Product Glycosylation

Karin M. Hoffmeister: Platelet Glycosylation: The "In and Outs" of Platelet Transfusion

Thomas Peters: Carbohydrate-Virus Interactions by NMR

Oral presentations selected from submitted abstracts:

José A. Cremata: Differential N-glycosylation of rhEPO in Goat Mammary Gland Cell Expressed in Cell Culture or in the Milk

Joseph J. Barchi, Jr.: Do Carbohydrate Coated Nanoparticles Have Antitumour Therapeutic Potential?

Session VI: Glycosylation in Health and disease - 1

Chair: Gerald W. Hart

Hudson Freeze: Congenital Disorders of Glycosylation: A Look Into the Crystal Ball

Tamao Endo: Defective Glycosylation in Muscular Dystrophy

Kensuke Miyake: Roles for a Novel Molecule PRAT4A in the Subcellular Distribution and Responsiveness of Toll-Like Receptors

Jens C. Jensenius: Structural, Functional and Clinical Aspects of the MBL Pathway (Lectin Pathway) of Complement Activation - An Innate Immune Defence System

Oral presentations selected from submitted abstracts:

Rita Gerardy-Schahn: The Golgi UDP-Xylose Transport is Essential for the Formation of O-Linked Xyl-Xyl-Glc Epitopes on Epidermal Growth Factor Like Domains

Posters: Glycosylation in Health and Disease

Authors present posters Nos. III-1 – III-35.

Session VII: Glycosylation in Health and disease - II

Chair: Pamela Stanley

Jamey D. Marth: Protein Glycosylation in Cellular Mechanisms of Health and Disease

James Dennis: Tumour Metabolism and Drug Sensitivity is Dependent on N-Glycan Processing

Paul Crocker: Siglecs as Modulators of Innate and Adaptive Immune Responses

Michael Pierce: Attenuation of a Specific Glycosylation Reaction in Breast Carcinoma Cells Inhibits Cell Migration and Invasiveness

Oral presentations selected from submitted abstracts:

Jan Holgersson: Recombinant Mucin-Type Fusion Proteins as Versatile Inhibitors of Protein-Carbohydrate Interactions

Kazuyuki Sugahara: Neuritogenic Activity and Mechanism of Brain Chondroitin/Dermatan Sulfate Hybrid Chains

Session VIII: Glycosylation in Health and disease - III

Chair: Henrik Clausen

Robert J. Desnick: Enzyme Replacement and Enhancement Therapies for Lysosomal Diseases

Philip Livingston: Most Carbohydrate Cancer Antigens Can be Made Immunogenic

Joy burchell: Changes in Mucin-type O-Glycosylation in Cancer

Rikard Holmdahl: Carbohydrates and T-cell Immunity

Closing  Lecture

Chair: Henrik Clausen

Ronald L. Schnaar: Glycans in Nervous System Stability and Axon Regeneration

Henrik Clausen: Closing Comments

For abstracts click here