Hybrid Inositol Glycan Analogues

San Jose State University, San Jose CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The inositol glycans (IGs) are small oligosaccharides that are released from insulin- sensitive cells upon treatment with insulin. IGs are able to elicit several insulin-like activities in these cells, including stimulation of lipogenesis, glycogen synthesis, aerobic metabolism, and glucose transport. These features make IGs potentially valuable for the treatment of type II diabetes. The IGs ability to stimulate aerobic metabolism may also make them useful in cancer therapy, because cancer cells evade apoptosis in part by switching to anaerobic metabolism. However IG's are complex structures and their potential for medical applications is severely limited by the difficulty in their preparation. This project seeks to identify new IG analogues that are much simpler to prepare, but that still retain useful biological activities. In Specific Aim 1, a small library of hybrid inositol glycan analogues (HIGAs) comprised of an inositol ring coupled to a non- carbohydrate moiety will be prepared. In Specific Aim 2, the synthetic HIGA library will be screened in cultured mammalian cells to identify HIGAs that warrant further development for the treatment of type II diabetes. In Specific Aim 3 the HIGA library will be evaluated for cytotoxicity in cultured human cancer cells and in non-cancerous cells to determine if any library members should be pursued for their anticancer activities. PUBLIC HEALTH RELEVANCE: Hybrid Inositol Glycan Analogues This project is relevant to public health because it seeks to identify new compounds that are active in stimulating insulin-sensitive cell types. Such compounds are expected to be useful in the treatment of both type II diabetes and cancer.