Mark Distefano, PhD

Distinguished McKnight Professor & Merck Professor, Department of Chemistry

Mark Distefano

Contact Info

Office Phone 612-624-0544

Fax 612-626-7541

Office Address:
668C Kolthoff Hall
207 Pleasant St. SE
Minneapolis, MN 55455

Mailing Address:
668C Kolthoff Hall
207 Pleasant St. SE
Minneapolis, MN 55455

Distinguished McKnight Professor & Merck Professor, Department of Chemistry

Graduate Faculty, Department of Medicinal Chemistry

PhD, Massachusetts Institute of Technology, 1989

BA, University of California, 1984


Research in the Distefano group focuses on the use of organic chemistry to provide insight into mechanism and function in biological systems. Several projects are currently being investigated including (1) mechanism and function of protein prenylation (2) rubber biosynthesis (3) illudin biosynthesis (4) protein-based catalyst design and (5) development of methods for selective protein modification. 

Two themes unite this diverse range of topics. The protein prenylation, rubber biosynthesis and illudin biosynthesis projects center around the use farnesyl diphosphate and analogues thereof. The goals of these projects are to identify the enzymes involved in these processes and to understand their chemical mechanisms for the purposes of designing new therapeutic agents or biocatalytic processes. The catalyst design and protein modification projects both involve the use covalent modification techniques to prepare proteins with either novel catalytic or physical properties.

Researchers in the Distefano group use a combination of organic synthesis, protein purification, enzymology and biophysical techniques as they work on these projects. Numerous collaborations are in place with other groups both at the University of Minnesota and other academic and industrial institutions to accomplish the interdisciplinary goals of these projects.


Chemical synthesis, biochemistry, enzymology, drug design, protein prenylation

Awards & Recognition

  • Ryerson Professor of Chemistry, 2016
  • ACS Fellow, 2014
  • Merck Professor of Chemistry, 2011
  • Distinguished McKnight Professor, 2011
  • Horace T. Morse–University of Minnesota Alumni Award, 2006
  • George W. Taylor/ITAS Award for Distinguished Teaching, 2004
  • American Cancer Society Junior Faculty Research Award, 1994
  • National Science Foundation CAREER Award, 1994


  • French


Research Summary/Interests

  • Enzymology
  • Protein Chemistry
  • Peptide Chemistry
  • Protein Prenylation
  • Photochemistry


  • Mullen, D.; Kyro, K.; Hauser, M.; Becker, J. M.; Naider, F.; Distefano, M. D. Synthesis of a-factor peptide from Saccharomyces cerevisiae and photoactive analogues via Fmoc solid phase methodology. Biorg. Med. Chem. 2011, 19, 490.
  • Rashidian, M.; Dozier, J. K.; Lenevich, S.; Distefano, M. D. Selective Labeling of Polypeptides Using Protein Farnesyltransferase via Rapid Oxime Ligation. Chem. Comm. 2010, 46, 8998. PMID: 20967387.
  • DeGraw, A. J.; Palsuledesai, C.; Ochocki, J. D.; Dozier, J. K.; Lenevich, S.; Rashidian, M.; Distefano, M. D. Evaluation of alkyne-modified isoprenoids as chemical reporters of protein prenylation. Chem. Bio. Drug. Des. 2010, 76, 460.
  • Wollack, J.; Silvermann, J.; Petzold, C.; Mougous, J.; Distefano, M. D., A Minimalist Substrate for Enzymatic Peptide and Protein Conjugation. ChemBiochem 2009, 10, 2934-2943.
  • Duckworth, B. P.; Chen, Y.; Sham, Y.; Mueller, J. D.; Taton, T. A.; Distefano, M. D., A Universal Method for the Preparation of Covalent Protein-DNA Conjugates for Use in Creating Protein Nanostructures. Angew. Chemie (Int. Ed) 2007, 46, 8819-8822.