Development of cell-based assays for discovery of GIcNAc-TV inhibitors.

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DESCRIPTION (provided by applicant): Malignant transformation induces changes in the structures of many glycans. One of the most consistent alterations observed in a wide range of cancers is the increased expression of beta 1,6 branched N-linked glycans. Genetic experiments and human clinical data have shown that beta 1,6 branched N-linked glycans directly promote cancer progression. The goal of this proposal is to develop a cell-based screening system to identify inhibitors of the biosynthesis of complex beta 1,6 branched N-linked glycans. Small molecule inhibitors of the biosynthesis of beta 1,6 branched N-linked glycans will be useful as tools to study the biological roles of these glycans and as starting points to develop novel anti-cancer agents. Relevant structural changes in N-linked glycans have been shown to be associated with malignant transformation and metastasis. Specifically, an increase in beta 1,6 branched N-linked glycans in tumors has been found to promote aggressive cancer progression. The goal of this proposal is to develop a system to identify small molecule inhibitors of the biosynthesis of complex beta 1,6 branched N-linked glycans for the development as a novel anti-cancer drugs.