Robert J. Hondal

Hondal photo

Robert J. Hondal, Ph.D., Associate Professor of Biochemistry & Chemistry

  • Ph.D., Ohio State University, Columbus, OH, 1997
  • postdoctoral fellowship, Vanderbilt University, Nashville, TN, 1997-98
  • postdoctoral fellowship, University of Wisconsin, 1999-2002
  • Assistant Professor of Biochemistry, College of Medicine, University of Vermont, 2002-08
  • Associate Professor of Biochemistry, College of Medicine, University of Vermont, 2008
  • Associate Professor of Chemistry, University of Vermont, 2010
  • Curriculum vitae
Contact Information


Phone: (802) 656-8282

Office: Given Bldg Rm B415

Areas of expertise

bioorganic chemistry, biochemistry, enzymology, protein function, selenium


There are two main areas of research in my lab. First, we are concerned with the mechanistic enzymology of high molecular weight thioredoxin reductases. The mammalian form of this enzyme contains the rare amino acid selenocysteine. One focus of this project is to understand why the mammalian enzyme requires this rare amino acid, while other homologues from C. elegans and D. melanogaster contain a conventional cysteine residue instead. We use protein engineering and protein semisynthesis techniques to study these enzymes. Semisynthesis allows us to insert a number of non-natural amino acids into the enzyme, as well as produce the mammalian form of the enzyme containing selenocysteine. X-ray crystallography, NMR spectroscopy, peptide synthesis, and steady-state kinetics are all techniques emphasized in my laboratory.

A second project involves developing new methods for regioselective disulfide bond formation in peptides and small proteins. A large challenge for peptide chemists is correctly pairing half-cystinyl residues. This is achieved through orthogonal protection/deprotection schemes using multiple protecting groups for the sulfhydryl group of cysteine. These groups are then selectively removed one at a time to form the correct disulfide bond.

Selected Publications

Snider G, Grout L, Ruggles EL, and Hondal RJ (2010) Methaneseleninic acid is a substrate for truncated thioredoxin reductase: Implications for the catalytic mechanism and redox signaling. Biochemistry 49, 10329-10338.

Lothrop, AP, Ruggles, EL, & Hondal RJ. (2009) No Selenium Required: Reactions Catalyzed by Mammalian Thioredoxin Reductase That Are Independent of a Selenocysteine Residue. Biochemistry 48, 6213-6223.

Hondal, RJ (2009) Using chemical approaches to study selenoproteins – focus on thioredoxin reductases. Biochim. Biophys. Acta 1790, 1501-1512.

Ruggles EL, Deker PB, & Hondal RJ. (2009) Synthesis, Redox Properties, and Conformational Analysis of Vicinal Disulfide Ring Mimics. Tetrahedron 65, 1257-1267.

Lacey BM, Flemer SJ, Eckenroth BE, & Hondal RJ (2008) Selenium in Thioredoxin Reductase: A Mechanistic Perspective. Biochemistry 47, 12810-12821.

Ruggles EL, Flemer SJ, & Hondal RJ (2008) A Viable Procedure for the Synthesis of N-Methyl Cysteine. Biopolymers 90, 61-68.

Flemer SJ, Lacey BM & Hondal RJ (2008) Synthesis of peptide substrates for mammalian thioredoxin reductase. J. Pept. Sci. 14, 637-47.

Eckenroth BE, Lacey BM, Lothrop AP, Harris KM, & Hondal RJ (2007) Investigation of the C-terminal Redox Center of High Mr Thioredoxin Reductases by Protein Engineering and Semisynthesis. Biochemistry 46, 9472-9483.

Eckenroth BE, Rould MA, Hondal RJ, & Everse SJ (2007) Structural and biochemical studies reveal differences in the catalytic mechanisms of mammalian and Drosophila melanogaster thioredoxin reductases. Biochemistry 46, 4694-4705.

Harris KM, Flemer S & Hondal RJ. (2007) Studies on deprotection of cysteine and selenocysteine side chain protecting groups. J. Pept. Sci. 13, 81-93.

Eckenroth BE, Harris K, Turanov AA, Gladyshev VN, Raines RT, & Hondal, RJ. (2006) Semisynthesis and characterization of mammalian thioredoxin reductase. Biochemistry 45, 5158-5170.

Ruggles EL, & Hondal RJ. (2006) Synthesis and properties of disulfide-bond containing eight-membered rings. Tet. Lett. 47, 4281-4284.

Lacey BM, & Hondal RJ. (2006) Characterization of mitochondrial thioredoxin reductase from C. elegans. Biochem. Biophys. Res. Commun. 346, 629-636.

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