Synthesis of unnatural substrates and ligands for biological investigation

Abstract

The use and modification of existing natural products have allowed for significant advances in science and engineering. Through synthetic alterations to these natural motifs, unnatural products allow access to new and interesting possibilities for experimental design. This work focuses on exploring the applications of chemically modified amino acids, carbohydrates, and flavonoids to current chemical and biological studies. Chemically modified 4-fluoro UDP-sugar analogs were used to synthesize heparin-like oligosaccharides with novel linkages for use in chain extension/termination studies. A small library of well-defined heparan sulfate (HS) polysaccharides was chemoenzymatically synthesized and used for a detailed structure-activity study of fibroblast growth factor (FGF) signaling. Additionally, a set of chiral polymeric membranes using modified amino acids was developed which allowed for selective protein separation and reduced fouling. Finally, a series of 5,7-dihydroxyflavanone derivatives were efficiently synthesized and their antimicrobial efficacy on Gram-negative, Gram-positive bacteria and yeast were evaluated. These studies demonstrate the value of continued exploration of the interface between synthetic chemistry and biology, where unnatural analogs of complex natural biological motifs continue to find valuable applications.