SBIR-STTR Award

In this Phase I grant application, the researchers propose to develop the synthesis of a series of inositolphospholipids, including 1d-1-(1-fattyacyl'-2-fattyacyl''-sn-glycero-3-phospho)-myo-inositols (phosphatidylinositols) and analogues. In eukaryotic cells, these compounds function as structural components of membranes and protein anchors, and are metabolic precursors of intracellular messengers. Practical approaches for the economical synthesis of these compounds are not available. During Phase I, the applicants will develop laboratory scale approaches, potentially adaptable for the economical larger scale preparation of phosphatidylinositols and analogues. PROPOSED COMMERCIAL APPLICATION: The methods will be used for commercial production and marketing of phosphatidylinositols for biomedical applications.

Inositolphospholipids are an important group of biological amphiphilic phospholipids. The group includes phosphatidylinositols (PtdIns) and its radyl and sphingo analogues. Members of the group are critical intracellular signaling messengers, and important as biomedical research reagents and for developing diagnostics and therapeutics based on signaling modalities. Furthermore, inositolphospholipids are biocompatible amphiphiles with applications in skin-care and intravenous drug delivery formulations. No practical approach adaptable for economical large scale production is available. The overall objective of this investigation is to develop laboratory scale methods of synthesis, potentially adaptable for economical larger scale production, for preparing individual molecular species of PtdIns and analogous inositolphospholipids. During Phase I, a novel approach, applicable to the entire biological PtdIns group and tailored analogues, was experimentally validated for PtdIns synthesis, and the structural and stereochemical integrity of the products was established unequivocally. During Phase II, this approach to synthesis will be optimized for ultimate economical larger scale production of PtdIns, and extended to radyl, sphingolipid, thiophosphate and phosphonate type analogues and selected diastereomers. Further, the approach will be exploited for the preparation of selected inositolphospholipid molecular species.