Membrane protein studies are severely limited by lack of efficient methods for their purification. IAM surfaces have recently been discovered and are extremely effective at purifying functional membranes proteins. Since IAM surfaces are prepared by covalently bonding membrane-forming-lipids to silica, the IAM chromatographic surface emulates the cell membrane's lipid environment. Consequently, IAM surfaces are also useful at predicting solute and/or drug transport across biological barriers.
The specific aims of Phase I studies are: (1) To prepare a wide pore (1000 Angstroms) version of the commercial IAM.PC for improved mass- transfer of large molecules; and (2) To transfer the recent technology developed by Dr. Pidgeon to Regis and commercialize two new IAM packings: the IAM.PC surface end-capped with alkylanhydrides, which sterically protect the silica surface from solvolysis; and an IAM surface containing a single ether-linked phospholipid. Dr. Pidgeon's eight step ether phospholipid synthesis will be scaled up for production and commercialization of IAM surfaces. The large scale lipid synthesis will provide the basis for the synthesis of additional IAM bonded phases with different membrane lipids during Phase II. This IAM surface diversity is expected to provide selectivity for many membrane proteins, thus effecting their purification.
