Version 2.1.1.0

Abstract

Grant Number:	1R43GM069074-01
PI Name:	NEILSEN, PAUL O.
PI Email:	pneilsen@echelon-inc.com
PI Title:
Project Title:	Hybrid Phospholipid-Phosphoinositides

Abstract: DESCRIPTION (provided by applicant): Phosphoinositide recognition by binding proteins and lipid-metabolizing enzymes involves specific interactions with the head group and diacylglycerol backbone, which vary significantly from protein to protein. When a fluorescent probe is introduced into the inositol head group, binding and metabolism are severely attenuated or abrogated entirely. When a fluorescent probe is introduced into the acyl groups, many of the resulting derivatives fail to show adequate Km and Vmax values as substrates for lipid kinases and phosphatases as well as binding to cognate PIP-binding proteins. Recently, Echelon Biosciences has developed a new approach to make phospholipid-phophoinositide hybrids based on a four-carbon threitol backbone. These new materials, known as Pea-PIPs TM, have a phosphatidylethanolamine head group that permits biochemical or chemical probes to be attached in a position spatially orthogonal to the phosphoinositide head group and the two acyl chains. In this Phase i grant, we will first synthesize a full repertoire of all eight Pea-PIPns TM. Second, we will prepare two Pea-PIPs TM with four different hydrophilic linker arms to optimize probe-head group distances. Third, we will establish the feasibility of using Pea- PIPs TM as in vitro substrates for lipid kinases, lipid phosphatases, and lipid binding proteins.

Thesaurus Terms:
chemical synthesis, phosphatidylinositol, technology /technique development
glycerophosphate, protein protein interaction, recombinant protein
fluorescence polarization, fluorescent dye /probe, protein purification

Institution:	ECHELON BIOSCIENCES, INC.
	675 ARAPEEN DR, STE 302
	SALT LAKE CITY, UT 84108
Fiscal Year:	2003
Department:
Project Start:	15-AUG-2003
Project End:	14-FEB-2004
ICD:	NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
IRG:	ZRG1

---