Researcher ORCID Identifier

0009-0005-2601-1028

Graduation Year

2024

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Chemistry

Reader 1

Nicholas D. Ball, Ph.D.

Reader 2

Roberto A. Garza-López, Ph.D.

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Terms of Use for work posted in Scholarship@Claremont.

Rights Information

© 2024 Pedro R. Martinez Velez

Abstract

In 2014, sulfur(VI) fluorides were reintroduced as connecting hubs, establishing Sulfur Fluoride Exchange as a novel reaction for click chemistry.4 Since their reintroduction, sulfur(VI) fluorides have extended the scope of multiple fields in chemistry.8 Advances in synthetic methodologies towards sulfur(VI) fluorides, including catalysis and solid-state reagents, have led to their application as tools in biomolecular and medicinal chemistry.46 In particular, aryl sulfonyl fluorides15 and aryl fluorosulfates29 have found a niche for addressing a major gap in knowledge in biochemistry: the functional annotation of proteins.34 In chemical biology, synthetic chemical probes are used to interrogate the reactivity of protein binding pockets.38 Sulfur(VI) fluorides have unique reactivity/stability, which makes them attractive as electrophilic reactive groups for chemical probe development.23 Nitrogen-containing sulfur(VI) fluorides have not been extensively researched as chemical probes. N-disubstituted sulfamoyl fluorides (NR1R2−SO2F) represent the lower reactivity limit of sulfur(VI) fluorides. This literature thesis has two aims: to propose the design of a set of N-disubstituted sulfamoyl fluorides, and to propose an experimental workflow for evaluating their potential as protein chemical probes. I hypothesize that, since N-disubstituted sulfamoyl fluorides have low intrinsic reactivity compared to other sulfur(VI) fluorides, they function as highly selective chemical probes for protein covalent modification. Finally, I propose the use of Inverse Drug Discovery to evaluate these probes, employing affinity chromatography-mass spectrometry for identification of potential protein targets for each probe.47, 52 This proposal would expand the potential of covalent drugs, by establishing N-disubstituted sulfamoyl fluorides as highly selective electrophilic groups for the covalent modification of proteins.

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