Year: 2024
Type: article
Abstract: The field of chemical biology has delivered diverse chemical tools that have been developed to answer fundamental biological questions. These chemical tools include small molecules, peptides, and oligonucleotides, which have been chemically modified for perturbing, profiling, modifying, and visualizing biomacromolecules. Herein, I detail my contributions to the fields of sulfotransferase biology and covalent protein modification through the development of small molecule- and oligonucleotide-based chemical tools to perturb, profile, and modify proteins. First, I describe the design and synthesis of novel isoform-specific allosteric inhibitors of two sulfotransferases, SULT1A3 and SULT2B1b, which regulate neurotransmitter and cholesterol metabolism, respectively. The allosteric inhibitors detailed within represent an entirely innovative approach to the inhibition of an ‘undruggable’ enzyme class that has immense implications in human diseases such as major depression, Alzheimer’s, and cancer. I then transition from small-molecule-based to nucleic acid-based tools, and present covalent aptamers as versatile tools for endogenous protein modification and inhibition. The aptamers are functionalized with cleavable electrophiles that transfer functional labels to nucleophilic residues on protein targets. My efforts have driven the extension of this protein labeling approach from a test tube to the cell surface, modifying cancer biomarkers for various biological applications.
Author: Cacace, Mary Frances
Institution: University of Pittsburgh
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W6999370232