Synthetic and analytical studies aimed at molecular recognition applications

Abstract

The creation of small molecule libraries for binding into the NS1A protein of influenza A viruses and the development of an indicator displacement assay for the differentiation of fatty acids are reported herein. Using Mitsunobu chemistry, a variety of structures based on hydroquinone, resorcinol and 2,7-dihydroxynaphthalene cores were synthesized. Both polar and non-polar functional groups were added to diversify the cores to help understand which molecule binds best to the protein. Because of poor protein binding, the focus of the project moved to a new lead compound, epigallocatechin-3-gallate (EGCG). EGCG showed promise in computational studies and efforts towards the synthesis of the epigallocatechin core were undertaken. Using a fluorescent indicator displacement assay (IDA), a sensing system for fatty acids was developed. The system consisted of bovine, rabbit, and human serum albumins as host molecules, while the fluorescent indicators were fluorescein, 2-anthracene carboxylic acid, and 1-anilino-8-naphthalene sulfonic acid. Fatty acids were able to be differentiated from one another based on their carbon chain length and the degree of unsaturation. The IDA was then subjected to a complex mixture of fatty acids, in the form of edible oils. The oils (extra virgin olive, hazelnut, peanut, sunflower and canola) with different fatty acid profiles were able to be differentiated from each other using principal component analysis.