SYSTEM AND METHOD FOR CREATING A SERIES OF THREE DIMENSIONAL GLYCAN STRUCTURES DATABASES AND THEIR APPLICATIONS

摘要

A database containing the three dimensional structures of unique fragments of glycan molecules that exist in nature. The glycans' fragments in the database are derived from given sets of glycans described by the linear representation of glycans (Dukler and Dotan 2000a) named the Linear Code(tm). The linear code utilizes an algorithm that creates and accounts for all possible unique glycan fragments and sorts these fragments. The structural information in the Database according to the present invention is accompanied by biological information obtained from the Glycomics database (Dukler and Dotan 2000b). Glycans are molecules that regularly interact with proteins during their enzymatic synthesis and function. Molecules that mimics glycans will interacts with glycan processing enzymes or glycan binding proteins (lectins). Therefore, one application of the database according to the present invention is ADME/Tox by identification of candidate drugs that will structurally mimic glycans. This is achieved by in silico assays of potential drug candidates. The structure of potential drug candidate molecules is compared to glycan fragments in a relevant cluster of the database. Molecules that have similar structural and chemical features to the glycan fragments are likely to interact with the binding sites of glycan processing enzymes or glycan binding proteins and cause unwanted toxicity, elimination and/or side effects. This method thus generates information which can be utilized to optimize the design of the drug candidate molecules.