KSEF RDE: Engineered Porous Thin Films for Screening and Production of Therapeutics Derived from Plant Biotechnology

Plants offer an extraordinary variety of bioactive small molecule metabolites that are potentially valuable as pharmaceuticals, nutraceuticals and agrochemicals because they bind to target receptor proteins in other organisms (e.g. for therapeutics, these would be human proteins). Recent advances in plant biotechnology have generated bioactive metabolites and developed approaches to modifying and producing bioactive ligands in plants that are not readily synthesized. However, current technologies to separate these bioactive ligands (both for identification and production) lag the novel methods which can be used to produce them, and therefore limit their commercial production. Potentially valuable ligands from plants are currently screened for bioactivity and concentrated based on the affinity (binding) of the ligand to a desired protein receptor, which has been immobilized on the surface of nonporous particles. The use of nonporous particles in affinity separations does not take advantage of the dramatically surface area, protein stabilization, and selective functionalization strategies that are possible in tailored nanoporous silica structures. The proposed work will develop porous thin film silica platforms for the immobilization of the human estrogen receptor (ER á/â), which binds potential therapeutics and anti-cancer agents. The benefits of receptor immobilization in pores will be quantified by measuring the capacity, selectivity, and stability of the protein receptor for model isoflavonoid ligands relative to surface-immobilized receptor proteins. A primary advantage of porous thin film platforms for sensor design (necessary for screening individual plant cultures) is sensitivity, where adsorption of ligands can be monitored directly from the mass change of the thin film using a Quartz Crystal Microbalance. Design strategies developed for thin films can be translated to porous silica particles for larger scale separation and bioactive ligand recovery, thus enabling rapid advances in discovery and production of plant-derived therapeutic compounds.