By Hillel Alpert

Glycomics: Glycans exhibit a branchlike structure because of multiple bonds at multiple sites; therefore, the study of protein-glycan interactions could become even more vast than proteomics.

Glycominds Ltd. founders Avinoam Dukler and Nir Dotan are tired of all the attention lavished on genes and proteins, to the neglect of complex carbohydrates. These substances, also known as glycans, play an essential role in countless biological pathways. They are involved in cell-to-cell interactions, infectious disease and immune functions, and protein function and regulation. At least half of the proteins in the human body cannot function properly without carbohydrates, and the sugars that are attached to therapeutic proteins can profoundly affect their pharmacological properties.

Dukler and Dotan coined the term "glycomics" in their business plan, referring to the systematic study of protein-glycan interactions and function, a body of data that could become even more voluminous than proteomics. That's because a complex sugar can have a multiplicity of bonds at multiple points, producing a tree-like branching structure, whereas a protein molecule features just a single peptide bond.

The glycome may therefore be thousands of times as complicated as the genome in terms of complexity and diversity. For example, some 15 million different tetrasaccharides, which are relatively simple glycans, could arise from just nine monosaccharide building blocks. Furthermore, each cell, tissue, organ, and organism exhibits different glycosylation patterns that can vary with the cell's state or activity.

Glycominds, based in Lod, Israel, confronts this challenge with its technology triad beginning with the Linear Code, a canonic syntax for representing 3-D glycan structures and their associated molecules, including branching, linkage, and/or terminal modifications. The code is expressed in a linear fashion without losing information, just as the primary sequences of proteins and DNA molecules are recorded.

This classification scheme enabled the compilation of the Glycomics Database with all the known information about glycol-conjugated molecules, including their structures, functions, and interactions with proteins and other molecules. Literature sources are associated with the database entries, which currently exceed 35,000. Much of the latest information focuses on the expression and function of glycans in inflammation, autoimmune diseases, and bacterial infections. With its unique search capabilities, the database is optimally used in conjunction with the Glycochip — a microarray for high-throughput analysis of complex carbohydrates.

These technologies are licensed for the identification of glycan-related biomarkers that predict individual drug responses to aid in selection of patients for clinical trials and pharmacoglycomic assays that can assist in diagnostics and in decisions to prescribe the best drug to the right patient. One such assay will identify in six to 12 hours bacterial infections that can lead to septic shock, compared with current diagnostics that take 24 to 48 hours.

The Glycochip also yields information about drug immunogenicity, toxicity, and efficacy to assess the potential success of drug compounds on an industrial scale. The next generation of the chip is being developed with SGT Inc., an American subsidiary of the Schott Group, using a glass substrate that will be more reliable, reduce nonspecific drug binding, and enhance the sensitivity and accuracy of the chip, Dukler says.

Content with providing tools for pharmaceutical companies, Glycominds is resisting the lure of becoming a drug discovery company. "To develop a new class or better drug is high-risk, long-term, and highly competitive," Dukler says. "We leverage our glycan-protein interactions knowledge based on the Glycochip technology in order to identify biomarkers and develop diagnostic kits. We are estimating that glycomics companies will take approximately 10 percent of a $7.5-billion bioinformatics market, mostly in pharmacogenomics and biochips, in 2002, and more than 30 percent in 2005."

As co-sponsor of the Consortium for Functional Glycomics, a National Institutes of Health glue grant recipient consisting of 54 international scientists, Glycominds provides approximately 4,000 annotated carbohydrate structures to a publicly searchable database.

Glycominds forged several key international business relationships before recent events in the Middle East discouraged travel to the region. "We are an Israeli company. We are not trying to pretend not to be," Dukler insists, pointing to Teva Pharmaceutical Industries Ltd. and Compugen Ltd. as two notable Israeli companies with international activity. He quips, "What is typically Israeli about our company is that we are used to sleeping in planes."

—Hillel Alpert 

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