Thomas C. Leeper

Thomas C. Leeper

Visiting Assistant Professor of Biochemistry and Molecular Biology

Department/Affiliation: BCMB, Biology, Chemistry
Phone: 330-287-1981
Office Address: 108 Morgan Hall
Curriculum Vitae (CV)


  • B.S., Biology, Truman State University (formerly Northeast Missouri State University), 1995
  • Ph.D., Biochemistry, University of Missouri-Columbia, 2001

Areas of Research

My group studies the structures of protein-protein, protein-nucleic acid, protein-metal ion, and peptide-metal ion complexes. Such complexes are often representative of chemical communication, molecular recognition, and/or drug-receptor interactions. Predominantly we use Nuclear Magnetic Resonance spectroscopy (NMR), but also routinely employ X-ray crystallographic, proteomic, biochemical, cytological, and synthetic techniques. Ultimately we wish use our analysis of complex formation and biomolecular structure to understand how inter-molecular complexes function in cell biology and disease. A number of specific topics are currently under investigation:

  • Proteins that bind to long non-coding RNA (lncRNA) and regulate epigenetic change.
  • RNA molecules that act as regulatory species such as microRNAs and G-quadruplex structures.
  • NMR methods for ortholog specific fragment-based drug discovery (FBDD).
  • Metalloprotein and organometallic-protein complexes for rational drug development.

Courses Taught

  • BCMB 331: Principles of Chemistry
  • BIOL 201: Gateway to Molecular and Cellular Biology

Awards and Professional Memberships

  • NIH Postdoctoral Fellowship, Ruth L. Kirschstein , Individual National Research Service Award (NRSA), 2004-2007
  • Albert G. Hogan Dissertation Award, University of Missouri Columbia, 2002
  • Molecular Biology Fellowship, University of Missouri, Columbia, 1995-1999
  • Missouri Higher Education Academic "Bright Flight" Scholarship, Truman State University, 1990-1995


  • Kim H, Poelling RR, Leeper TC, Meyer MA, Schmidt FJ. “In vitro transactivation of Bacillus subtilis RNase P RNA.” FEBS Letters 506, 235-238 (2001).
  • Leeper TC, Martin MB, Kim H, Cox S, Semenchenko V, Schmidt FJ, Van Doren SR. “Structure of the UGAGAU hexaloop that braces Bacillus RNase P for action.” Nature Structural Biology 9, 397-403 (2002).
  • Leeper TC, Leulliot N, and Varani G. “The solution structure of an essential stem-loop of human telomerase RNA.” Nucleic Acids Research 31, 2614-2621 (2003)
  • Leulliot N, Quevillon-Cheruel S, Graille M, van Tilbeurgh H, Leeper TC, Godin KS, Edwards TE, Sigurdsson STh, Rosenkrantz N, Nagel RJ, Ares M, and Varani G. “A new alpha-helical extension promotes RNA binding by the dsRBD of Rnt1p RNAse III.” EMBO J. 23, 2468-2477 (2004).
  • Varani G, Chen Y, and Leeper TC. “NMR Studies of Protein-RNA Interactions.” Methods in Molecular Biology 278, 289-312 (2004).
  • Leeper TC and Varani G. “The structure of an enzyme activating fragment of human telomerase RNA.” RNA 11, 394-403 (2005).
  • Leeper TC, Athanassiou Z, Dias RL, Robinson JA, and Varani G, “TAR RNA recognition by a cyclic peptidomimetic of Tat protein.” Biochemistry 44, 12362-12372 (2005).
  • Davidson A, Leeper TC, Athanassiou Z, Patora-Komisarska K, Karn J, Robinson JA, and Varani G. “Simultaneous recognition of HIV-1 TAR RNA bulge and loop sequences by cyclic peptide mimics of Tat protein.” Proceedings of the National Academy of Sciences of the United States of America, 106, 11931-11936 (2009).
  • Leeper TC, Qu X, Lu C, Moore C, Varani G. “Novel protein-protein contacts facilitate mRNA 3'-processing signal recognition by Rna15 and Hrp1.” Journal of Molecular Biology 401, 334-349 (2010).
  • Lunde BM, Reichow SL, Kim M, Suh H, Leeper TC, Yang F, Mutschler H, Buratowski S, Meinhart A, Varani G. “Cooperative interaction of transcription termination factors with the RNA polymerase II C-terminal domain.” Nature Structural and Molecular Biology 17, 1195-1201 (2010)
  • Bilinovich SM, Panzner MJ, Youngs WJ, and Leeper TC. “Poly[[{u3-2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonato}silver(I)] trihydrate],” Acta Crystallographica Section E: Structure Reports, E67, (2011)
  • Leeper TC, Zhang S, Van Voorhis WC, Myler PJ, and Varani G. “Comparative analysis of glutaredoxin domains from bacterial opportunistic pathogens.” Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 67 1141-1147 (2011)
  • Brinkley SL, Leeper TC, Rowlett RS, Herrick RS, and Ziegler CZ. “Re(CO)3(H2O)3+ binding to lysozyme: structure and reactivity.” Metallomics 3, 909-916 (2011)
  • Panzner MJ, Bilinovich SM, Youngs WJ, and Leeper TC. “Silver metallation of hen egg white lysozyme: X-ray crystal structure and NMR studies.” Chemical Communications 47, 2479-81 (2011)
  • Prokop JW, Leeper TC, Duan ZH, and Milsted A. “Amino acid function and docking site prediction through combining disease variants, structure alignments, sequence alignments, and molecular dynamics: a study of the HMG domain.” BioMed Central Bioinformatics 13, Suppl 2:S3 (2012)
  • Morris MJ, Wingate KL, Silwal J, Leeper TC, and Basu S. “The porphyrin TmPyP4 unfolds the extremely stable G-quadruplex in MT3-MMP mRNA and alleviates its repressive effect to enhance translation in eukaryotic cells.” Nucleic Acids Research 40, 4137–4145 (2012)
  • Blackledge TA, Kuntner M, Marhabaie M, Leeper TC, and Agnarsson I. “Biomaterial evolution parallels behavioral innovation in the origin of orb-like spider webs.” Scientific Reports 2, 833 (2012).
  • Panzner MJ, Bilinovich SM, Parker JA, Bladholm EL, Ziegler CJ, Berry SM, and Leeper TC. “Isomorphic deactivation of a Pseudomonas aeruginosa oxidoreductase: The crystal structure of Ag(I) metallated azurin at 1.7 Å.” Journal of Inorganic Biochemistry 128, 11-16 (2013)
  • Wu J, Zhao C, Hu R, Lin W, Wang Q, Zhao J, Bilinovich SM, Leeper TC, Li L, Cheung HM, Chen S, and Zheng J. “Probing the weak interaction of proteins with neutral and zwitterionic antifouling polymers.” Acta Biomaterialia 10, 751-760 (2014).
  • Marhabaie M, Leeper TC, and Blackledge TA. “Protein Composition Correlates with the Mechanical Properties of Spider (Argiope trifasciata) Dragline Silk.” Biomacromolecules 15, 20-29 (2014).
  • Herrick RS, Ziegler CJ, and Leeper TC. “Structure and function in organometallic•protein complexes.” Journal of Organometallic Chemistry 751, 90-110 (2014).
  • Bilinovich SM, Davis, CM, Morris DL, Ray LA, Prokop JW, Buchan GJ, and Leeper TC. “The C-terminal domain of SRA1p has a fold more similar to PRP18 than to an RRM and does not directly bind to the SRA1 RNA STR7 region.” Journal of Molecular Biology 426, 1753-1765, (2014).
  • Geldenhuys WJ, Leeper TC, and Carroll RT “mitoNEET as novel drug target for mitochondrial dysfunction.” Drug Discovery Today, May 9. pii: S1359-6446(14)00165-2 (2014).
  • Chanawanno K, Caporoso J, Kondetti V, Paruchuri SM, Leeper TC, Herrick RS, and Ziegler CJ “Facile solid phase peptide synthesis with a Re-lysine conjugate generated via a one-pot procedure.” Dalton Transactions, 43:11452-11455 (2014).
  • Zampino AP, Masters FM, Bladholm EL, Panzner MJ, Berry SM, Leeper TC, and Ziegler CJ “Mercury metallation of the copper protein azurin and structural insight into possible heavy metal reactivity” Journal of Inorganic Biochemistry, 141C: 152-160 (2014).
  • Prokop JW, Petri V, Shimoyama ME, Watanabe I, Caserini DE, Leeper TC, Bilinovich SM, Jacob H, Santos R, Martins AS, Araujo FC, Reis FM, and Milsted A. “Structural libraries of protein models for multiple species to understand evolution of the renin-angiotensin system” General and Comparative Endocrinology, 215: 106-116 (2015).
  • Martin M, Leeper TL.*, and Schmidt FJ “Transactivation of RNase P to Determine Structure-Function Relationships.” Methods in Molecular Biology, 1240:57-62. (2015). *corrected as Leeper TC in erratum (2015; 1240:E1).
  • Benson S, Boyce K, Bunker R, Collins N, Daily, K, Esway A, Gilmore G, Hartzler C, Howard G, Kasmar N, Kennedy K, King B, Kordahi T, Mattioli T, Pugh D, Ray L, Ross S, Torcasio M, Webber D, Morris DM, Leeper TC “Multinuclear NMR and UV-Vis spectroscopy of site directed mutants of the diabetes drug target protein mitoNEET suggest that folding is intimately coupled to iron-sulfur cluster formation.” Inorganic Chemistry Communications, 63: 86-92. (2016).
  • Chanawanno K, Kondti V, Caporoso J, Parachuri S, Leeper TC, Herrick RS, and Ziegler CJ “Facile rhenium–peptide conjugate synthesis using a one-pot derived Re(CO)3 reagent” Dalton Transactions, 45: 4729-35 (2016).
  • Khattri RB, Morris DL, Davis CM, Bilinovich SM, Caras AJ, Panzner MJ, Debord MA, Leeper TC “An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.” Molecules, pii: E846 (2016).,