William (Will) Parsons

Chemical biology, small-molecule synthesis, intramembrane hydrolases

Enzyme-mediated hydrolysis is a ubiquitous component of numerous metabolic pathways in the body. Nature has developed a number of chemistries within hydrolase active sites to cleave a diverse array of biological substrates. The Parsons lab studies enzymes that use serine and threonine residues to catalyze turnover of their substrates. A subset of these enzymes with intramembrane active sites are of particular interest due to their unique biochemistry as well as their involvement in pathways underlying metabolic and neurological diseases, including Parkinson’s disease and type 2 diabetes. 

The Parsons lab exploits the active site chemistry of these hydrolases to create new chemical probes for this enzyme class. Drawing upon methodology from synthetic chemistry, biochemistry, molecular biology, and medicinal chemistry, research in the Parsons lab focuses on the development of small molecule tools to study the physiological roles of intramembrane hydrolases.

Prof. Parsons teaches general and organic chemistry courses in the department. During the fall semester of 2023, he will be teaching both lecture sections of CHEM 205: Principles of Organic Chemistry. He will be on leave during the spring semester of 2024.

(Note: An asterisk indicates an Oberlin student/graduate co-author)

• Parsons WH, Cravatt BF. "Activity-based protein profiling." In Advanced Chemical Biology: Chemical Dissection and Reprogramming of Biological Systems; Hang HC, Pratt MR, Prescher JA, Eds; Wiley-VCH, 2023; pp 503–526.
• Wang X, Lin Z, Bustin KA, McKnight NR, Parsons WH, Matthews ML. “Discovery of potent and selective inhibitors against protein-derived electrophilic cofactors.” J Am Chem Soc. 2022, 144, 5377–5388. doi: 10.1021/jacs.1c12748.
• Parsons WH, Rutland NT*, Crainic JA*, Cardozo JM*, Chow AS*, Andrews CL*, Sheehan BK*. Development of succinimide-based inhibitors for the mitochondrial rhomboid protease PARL. Bioorg Med Chem Lett. 2021, 49, 128290. doi: 10.1016/j.bmcl.2021.128290.
• Lin Z, Wang X, Bustin KA, Shishikura K, McKnight NR, He L, Suciu RM, Hu K, Han X, Ahmadi M, Olson EJ, Parsons WH, Matthews ML. Activity-based hydrazine probes for protein profiling of electrophilic functionality in therapeutic targets. ACS Cent Sci. 2021, 7, 1524–1534. doi: 10.1021/acscentsci.1c00616.
• Parsons WH, Kolar MJ, Kamat SS, Cognetta AB III, Hulce JJ, Saez E, Kahn BB, Saghatelian A, Cravatt BF. AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs. Nat Chem Biol. 2016, 12, 367–372. doi: 10.1038/nchembio.2051.

Complete List of Publications