Novel Polymer Adsorbents for Selective Peptide and Small Protein Separations from Blood

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Proposal Number: 1604170, GuzmanNovel Adsorbents for Selective Peptide and Small Protein Separations from Blood Small biomolecules or biomarkers from human blood or other biological fluids such as urine are usually found in trace amounts. Their identification and purification is in general hindered by the high concentration of human albumin and other proteins found in blood and biological fluids. The effective recovery and identification of these biomolecules from complex biological mixtures has been until now a considerable challenge. The methods developed in this research will allow the effective isolation of bioactive peptides, hormones, and biomarkers that can be used in biomedical areas. This research will enable medical applications that isolate and remove toxins from biological fluids and then identify biomarkers for early cancer detection. In this research, selective adsorbents with polymers that do not allow the adsorption of large proteins will be synthesized. The adsorbents will be modified with chemical groups that will permit only the selective adsorption, from complex mixtures of targeted bioactive peptides, hormones and biomarkers that are found only at low concentrations. The technology will be tested in samples from biological fluids such as blood, urine and saliva. Studies will be conducted to obtain higher purification rates for targeted biomolecules. This will translate into lower operation costs in the development and discovery of new biomarkers and in the detoxification and cleaning of human blood. This project will be interdisciplinary in nature, the engineering, biology, and chemical knowledge used and gained in this research will be of interest to many disciplines. This program will involve undergraduate and graduate students from different disciplines with interest in chemistry, molecular biology, medicine, material sciences and chemical engineering.Despite many efforts to develop efficient protein purification techniques, the isolation of peptides and small proteins on a larger than analytical scale remains a significant challenge. There is currently no similar separation product commercially available. The primary objective of this research will be the development and characterization of a chromatographic adsorbent that allows separation of peptides and biomolecules by simultaneous specific adsorption, and size exclusion using polysaccharide matrices modified with permeation control polymers. This will be accomplished by grafting in chromatographic matrices two different heterogeneous ligands, one, a polymer such as polyethylene glycol that permits the permeation of only certain molecular size range compounds, and a second one, an affinity ligand such as a chelating agent or an ion exchange group that preferentially binds target biomolecules of that specific molecular size range that could cross the restricted polymer barrier. This method will eliminate competition for adsorptive sites on the matrix surface, between large and small molecules, thus increasing adsorption rate and capacity and effective separations and purifications of desired biomolecules. To effectively characterize the properties of these new matrices, systematic dual surface synthesis functionalization protocols will be developed using polyethylene glycol of different sizes and densities as the permeating polymer and chelating and ion exchange groups as affinity ligands.