Biodesign Directory Profile

Contact Information


John Chaput, PhD


The Biodesign Institute, Personalized Diagnostics


College of Liberal Arts and Sciences, Chemistry and Biochemistry


Visit the Chaput lab website.

Professor, Department of Chemistry and Biochemistry.
Professor, The Biodesign Institue

Prof. Chaput joined the faculty at ASU in January of 2005 after completing his Post-Doctoral Fellowship in molecular biology and genetics at Harvard Medical School.

Chaput applies the principles of natural selection to evolve functional molecules in the laboratory. This methodology (also referred to as test tube evolution) makes it possible to create artificial molecules with tailor-made properties. 

One fundamental question that Chaput is attempting to address is whether nature sampled all possible protein folds or just a small subset of the possible protein folds that are available in the protein universe. Through a process of in vitro selection and structure determination, Chaput is identifying new protein folds with specific, pre-defined functions. This approach of de novo protein evolution has the potential to create tailor-made proteins for biotechnology and molecular medicine.

Chaput is also interested in uncovering hidden proteins that remain buried in the shadows of the human genome. Using an integrated experimental-bioinformatics approach, Chaput is examining human DNA for sequences that enhance the translation of new proteins. This project has the potential to dramatically expand our current understanding of how genetic information is encoded in the genome. 

Lastly, Chaput is developing artificial affinity reagents that recognize human proteins with high affinity and specificity, but overcome or avoid many of the problems associated with traditional antibodies. This approach has the potential to dramatically improve the rate at which high quality protein affinity reagents are generated to human proteins. 

Selected Publications


  • Chaput, J.C.. Replicating an expanded genetic alphabet in cells. ChemBioChem (2014) Refereed Articles.
  • Chaput, J.C.. The Protein Capture Reagents Constortium, The challenge of antibody reproducibility: the solution lies in the sequence. Nature (2014) Refereed Articles.
  • Dunn, M.R., Larsen, A.C., Fahmi, N., Zahurancik, W.J., Meyers, M., Suo, Z., and Chaput, J.C.. Therminator-mediated synthesis of unbiased TNA polymers requires 7-deazaguanine to suppress G-G mispairing during TNA transcription. Journal of American Chemical Society (2014) Refereed Articles.
  • Larsen, A.C., Gillig, A., Shah, P., Sau, S.P., Fenton, K.E., and Chaput, J.C.. A general approach for characterizing in vitro selected peptides with high protein binding affinity. Analytical Chemistry (2014) Refereed Articles.
  • Martin Egli, Piet Herdewijn, Akira Matsuda, Yogesh S. Sanghvi, Serge L. Beaucage, Donald E. Bergstrom, Gary D. Glick, and Roger A. Jones (Eds), Dunn, M.R. and Chaput, J.C.. Current Protocols in Nucleic Acid Chemistry. An in vitro selection protocol for threose nucleic acid (TNA) using DNA display. (2014) Book Chapters.
  • Sau, S., Larsen, A.C., and Chaput, J.C.. Automated solid-phase synthesis of high capacity oligo-dT cellulose for affinity purification of short poly-A tagged biomolecules. Bioorganic & Medicinal Chemistry Letters (2014) Refereed Articles.
  • Saul, J., Petritis, B., Sau, S., Rauf, F., Gaskin, M., Ober-Reynolds, B., Mineyev, I., Magee, M., Chaput, J.C., Qiu, J., and LaBaer, J.. Development of a full-length human protein production pipeline. Protein Science (2014) Refereed Articles.


  • Korch, S.B., Stomel, J.M., Leon, M.A., Hamada, M.A., Stevenson, C.R., Simpson, B.W., Gujulla, S.K., and Chaput, J.C.*. ATP sequestration by a synthetic ATP-binding protein leads to novel phenotypic changes in Escherichia coli.. ACS Chemical Biology (2013) Refereed Articles.
  • Wellensiek, B.P., Larsen, A., Flores, J., Jacobs, B.L., and Chaput, J.C.*. A novel leader sequence capable of rapid and high protein synthesis in mammalian cells.. Protein Science (2013) Refereed Articles.
  • Wellensiek, B.P., Larsen, A., Stephens, B., Kukurba, K., Waern, K., Briones, N., Liu, L., Snyder, M., Jacobs, B.L., Kumar, S., and Chaput, J.C.*. Genome-wide profiling of human cap-independent translation enhancing elements. Nature Methods (2013) Refereed Articles.
  • Yu, H., Zhang, S., Dunn, M.R., and Chaput, J.C.*. An efficient and faithful in vitro replication system for threose nucleic acid.. J. Am. Chem. Soc. (2013) Refereed Articles.
  • Zhang, S. and Chaput, J.C.*. Synthesis and enzymatic incorporation of a-L-threofuranosyl adenine triphosphate (tATP). Bioorg. Med. Chem. Lett. (2013) Refereed Articles.
  • Zhang, S. and Chaput, J.C.*. Synthesis of Threose Nucleic Acid (TNA) Triphosphates and Oligonucleotides by Polymerase-mediated Primer Extension. Curr. Protoc. Nucleic Acid Chem. In Press.. Curr. Protoc. Nucleic Acid Chem. (2013) Refereed Articles.


  • Chaput, J.C.*, Hanyang, Y., and Zhang, S.. The emerging world of synthetic genetics.. Chem. & Biol. (2012) Refereed Articles.
  • Hanyang, Y., Zhang, S., and Chaput, J.C.. Darwinian Evolution of an Alternative Genetic System Provides Support for TNA as an RNA Progenitor. Nature Chemistry (2012) Refereed Articles.
  • Kang, M., Heuberger, B., Chaput, J.C., Switzer, C., and Feigon, J.. Solution structure of a parallel-stranded oligoisoguanosine DNA pentaplex formed by d(T(iG4)T) in the presence of Cs+ ions.. Angew. Chem. Int. Ed. (2012) Refereed Articles.
  • Martin Egli & Piet Herdewijn (Eds.), S. Zhang, C. Switzer, and J.C. Chaput. Chemistry and Biology of Artificial Nucleic Acids. The Resurgence of Acyclic Nucleic Acids (2012) Book Chapters.
  • Pinheiro, V.B., Taylor, A.I., Cozens, C., Abramov, M., Renders, M., Zhang. S., Chaput, J.C., Wengel, J., Peak-Chew, S-Y., McLaughlin, S.H., Herdewijn, P., and Holliger, P.. Synthetic Genetic Polymers Capable of Heredity and Evolution. Science (2012) Refereed Articles.
  • Zhang, S. and Chaput, J.C.. Synthesis of Threose Nucleic Acid (TNA) Phosphoramidite Monomers and Oligonucleotide Polymers. Curr. Protoc. Nucleic Acid Chem (2012) Refereed Articles.


  • H. Yu, B. Jiang, and J. C. Chaput. Aptamers can Discriminate Alkaline Proteins with High Specificity.. ChemBioChem (2011) Refereed Articles.
  • R. Liu, B. Jiang, H. Yu, and J. C. Chaput. Generating DNA Synbodies from Previously Discovered Peptides.. ChemBioChem (2011) Refereed Articles.


  • J. Zhang, B.A.R. Williams, M. Nilsson, J.C. Chaput. The Evolvability of Lead Peptides from Small Library Screens. Chem. Comm (2010) Refereed Articles.
  • Jeff Braman (Editor), McCullum, E.O., Williams, B.A.R., Zhang, J., and Chaput, J.C.. In Vitro Mutagenesis Protocols (volume 3). Random Mutagenesis by Error-Prone PCR (2010) Book Chapters.
  • S. Zhang, C. Switzer, and J.C. Chaput. The Resurgence of Acyclic Nucleic Acids. Chem. Biodiversity (2010) Refereed Articles.
  • Simmons, C.R., Magee, C.L., ?Smith, D.A., Lauman, L., Chaput, J.C. and Allen, J.P. Implications of Unusual Ligand Binding in a Synthetic Class of De Novo Proteins.. Biochemistry (2010) Refereed Articles.
  • Williams, B. A. R. and Chaput, J. C.. Synthesis of Peptide-Oligonucleotide Conjugates using a Heterobifunctional Crosslinker. Curr. Protoc. Nucleic Acid Chem. (2010) Refereed Articles.
  • Zhang, S. and Chaput, J. C.. Synthesis of Glycerol Nucleic Acid (GNA) Phosphoramidite Monomers and Oligonucleotide Polymers.. Curr. Protoc. Nucleic Acid Chem. (2010) Refereed Articles.


  • Lin, L., Fu, Q., Williams, B. A. R., Azzaz, A. M., Shogren-Knaak, M. A., Chaput, J. C., and Lindsay, S. M.. Recognition of Acetylated Chromatin Using a DNA Aptamer. Biophys. J. (2009) Refereed Articles.
  • Lin, S., Horning, D. P., Szostak, J. W., and Chaput, J. C.. Conformational Analysis of DNA Repair Intermediates by Time-Resolved Fluorescence Spectroscopy. J. Phys. Chem. (2009) Refereed Articles.
  • McCullum, E. O. and Chaput, J.C.. Transcription of an RNA Aptamer by a DNA Polymerase. Chem. Comm. (2009) Refereed Articles.
  • Simmons, C. R., Stomel, J. M., McConnell, M. D., Smith, D. A., Watkins, J. L., Allen, J. P., and Chaput, J. C.. A Synthetic Protein Selected for Ligand Binding Affinity Mediates ATP Hydrolysis. ACS Chemical Biology (2009) Refereed Articles.
  • Stearns, L. A., Chhabra, R., Sharma, J., Liu, Y., Petuskey, W. T., Yan, H., and Chaput, J. C.. Template-Directed Nucleation and Growth of Inorganic Nanoparticles on DNA Scaffolds. Angew. Chem. Int. Ed. (2009) Refereed Articles.
  • Stomel, J. M., Wilson, J. W., Leon, M. A., Stafford, P., and Chaput, J. C.. A Man-made ATP-Binding Protein Evolved Independent of Nature Causes Abnormal Growth in Bacterial Cells. PLoS ONE (2009) Refereed Articles.
  • Williams, B.A.R, Lin, L., Lindsay, S.M., and Chaput, J.C.. Evolution of a Histone H4-K16 Acetyl-Specific DNA Aptamer. J. Am. Chem. Soc. (2009) Refereed Articles.
  • Williams, B.A.R., Diehnelt, C.W., Belcher, P., Greving, M., Woodbury, N.W., Johnston, S.A., and Chaput, J.C.. Creating Protein Affinity Reagents by Combining Peptide Ligands on Synthetic DNA Scaffolds.. J. Am. Chem. Soc. (2009) Refereed Articles.


  • Chaput, J.C., Woodbury, N.W., Stearns, L.A., and Williams, B.A.R.. Creating protein biocatalysts as tools for future industrial applications.. Expert Opin. Biol. Ther. (2008) Refereed Articles.
  • Watkins, J. and Chaput, J.C.. Searching Combinatorial Libraries for Native Proteins with Novel Folds.. ChemBioChem. (2008) Refereed Articles.
  • Zhang, S., McCullum, E.O., and Chaput, J.C.. Synthesis of Two Mirror Image 4-Helix Junctions Derived from Glycerol Nucleic Acid.. J. Am. Chem. Soc. (2008) Refereed Articles.


  • Lin, L., Hom, D., Lindsay, S.M., and Chaput, J.C.. In Vitro Selection of Histone H4 Aptamers for Recognition Imaging Microscopy.. J. Am. Chem. Soc. (2007) Refereed Articles.
  • Mansy, S.S., Zhang, J., Kummerle, R., Nilsson, M., Chou, J.J., Szostak, J.W., and Chaput, J.C.. Structure and Evolution of a Non-Biological ATP Binding Protein. Journal of Molecular Biology (2007) Refereed Articles.
  • Smith, M.D., Rosenow, M.A., Wang, M., Allen, J.P., Szostak, J.W. and Chaput, J.C.. Structural Insights into the Evolution of a Non-Biological Protein: Importance of Surface Residues in Protein Fold Optimization. PLoS ONE (Public Library of Science) (2007) Refereed Articles.
  • Williams, B.A.R., Lund, K., Liu, Y., Yan, H. and Chaput, J.C.. Self-Assembled Peptide Nanoarrays: A New Approach to Studying Protein-Protein Interactions.. Angewandte Chemie International Ed. (2007) Refereed Articles.
  • Yang, Y-W., Zhang, S., McCullum, E., and Chaput, J.C.. Experimental Evidence that GNA and TNA are not Sequential Polymers in the Prebiotic Evolution of RNA.. Journal of Molecular Evolution (2007) Refereed Articles.


  • A Horhota, Z Keyong, J Ichida, L McLaughlin, J Szostak, John Chaput. Kinetic Analysis of an Efficient DNA-Dependent TNA Polymerase. J. Am. Chem. Soc (2005) Refereed Articles.
  • M Nilsson, J Stomel, John Chaput. Evolutionary Optimization of a De Novo Selected ATP Binding Protein. Biopolymers (2005) Refereed Articles.


  • John Chaput, J Szostak. Evolutionary Optimization of a Non-Biological ATP-Binding Protein for Improved Folding Stability. Chemistry & Biology (2004) Refereed Articles.


  • John Chaput, J Ichida, J Szostak. DNA Polymerase-Mediated DNA Synthesis on a TNA Template. J. Am. Chem. Soc (2003) Refereed Articles.
  • John Chaput, J Szostak. DNA Polymerase-Mediated TNA Synthesis. J. Am. Chem. Soc (2003) Refereed Articles.


  • John Chaput, S Sinha, C Switzer. 5-Propynyluracil diaminopurine: an efficient basepair for non-enzymatic transcription of DNA. Chem. Comm (2002) Refereed Articles.


  • John Chaput, C Switzer. Probing DNA Structure and Function with Alternative Nucleic Acids Bearing 2',5'-Linked, Zwitterionic and iso-Cytosine iso-Guanine Components. Methods: A Compendium to Methods in Enzymology (2001) Nonrefereed Articles.


  • John Chaput, C Switzer. Non-enzymatic Oligomerization on Templates Containing Phosphodiester-Linked Acyclic Glycerol Nucleic Acid Analogues. J. Mol. Evol (2000) Refereed Articles.
  • John Chaput, C Switzer. Non-enzymatic Transcription of an isoG:isoC Base Pair. J. Am.Chem. Soc (2000) Refereed Articles.
  • K Rice, John Chaput, M Cox, C Switzer. RecA Protein Promotes Strand Exchange with DNA Substrates Containing isoGuanine and 5-Methyl isoCytosine. Biochemistry (2000) Refereed Articles.