Research and drug development in the pharmaceutical industry rely upon synthetic chemistry and separation science. Oligonucleotide, peptide, and many combinatorial syntheses use solid-supported and automated synthetic methods. Analytical methods used today require the separation of analyte from other molecules, based upon interactions with a solid support. In these synthetic and analytical applications, there must be an interaction of reagents in solution with molecules attached to a solid material. The diffusion of a molecule from solution through the stagnant boundary layer at the solid-liquid interface to the immobilized molecule is a rate-limiting step. Boundary diffusion limits compromise the kinetics and efficiency of the solute's interaction with the immobilized species. The long-term objective of this research is to develop composite support materials that are not diffusion limited and will have unprecedented reaction and equilibration kinetics approaching those of solution phase processes. The Specific Aims of this Research are to synthesize a series of composite columns with functional groups immobilized by extended tethers that place the functional molecule thousands of Angstroms from the surface of the solid phase. The utility and kinetic characteristics of the tethered functional groups will be measured for the solid-phase synthesis of oligonucleotides and high speed chromatography of proteins. PROPOSED COMMERCIAL APPLICATIONS: The composite materials developed in this Research will find commercial use as products used for solid phase synthesis and for chromatographic separations and bioassay. The use of these products by the pharmaceutical and healthcare research industries will enable cost reductions, enhanced accuracy, and productivity increases in research to cure human disease.
