AMY M BARRIOS portrait
  • Professor, Department Of Biochemistry
801-581-3198

Research Statement

Our lab addresses topics at the interface between chemistry and biology, with an emphasis on exploring the chemical basis for the effects exerted by small molecules including metal ions in complex biological systems. Current projects include: 1) PROBING THE SUBSTRATE SPECIFICITY OF PROTEIN TYROSINE PHOSPHATASES We have recently developed a series of phosphotyrosine mimics that can be incorporated into peptide substrates and provide a highly sensitive fluorogenic assay for phosphatase activity. The novel probes have been introduced into living cells and will allow imaging of tyrosine phosphorylation and dephosphorylation in vivo for the first time. We also use substrate libraries to design PTP-selective substrates and incorporating these fluorogenic substrates into cells for use as intracellular assays for enzyme activity and inhibition. 2) INVESTIGATING THE ANTIARTHRITIC ACTIVITY OF AU(I) Gold has been used in the treatment of rheumatoid arthritis (RA) for over 80 years, but little is known about its mechanism of action. Current research efforts include elucidating the structure-activity relationship of Au(I)-mediated enzyme inhibition and examining both in vitro and in vivo enzyme inhibition by Au(I). Ultimately, our innovative interdisciplinary approach will provide an in-depth understanding of the principles governing Au(I)-biomolecule interactions, which will be used in the design of novel gold-based therapeutics.

Presentations

  • Invited speaker, Second Canadian Conference on Biological Inorganic Chemistry. (Research Assistant Professor Divya Krishnamurthy spoke in my stead). Parry Sound, ON Canada. Invited Talk/Keynote, Other, 05/25/2009.
  • Invited speaker, Brigham Young University Department of Molecular and Microbiology. Invited Talk/Keynote, Presented, 04/09/2009.
  • Poster presented at the 237th American Chemical Society National Meeting Salt Lake City, UT . Poster, Presented, 03/22/2009.
  • Invited speaker, Gordon Research Conference on Bioorganic Chemistry “Chemical Probes Put Phosphotyrosine-Dependent Cellular Signaling in the Spotlight” Andover, NH June 15-20, 2008. Invited Talk/Keynote, Presented, 2008.
  • Invited speaker, Northwest and Rocky Mountain Regional Meeting of the American Chemical Society. Postdoctoral Researcher Dr. Divya Krishnamurthy spoke in my stead. Park City, UT June 15-18, 2008. Invited Talk/Keynote, Other, 2008.

Research Groups

  • Vanessa Ahmed, Postdoc. 01/01/2009 - 04/30/2013.

Languages

  • English, fluent.

Publications

  • Identifying Potent, Selective Protein Tyrosine Phosphatase Inhibitors from a Library of Au(I) Complexes MR Karver, D Krishnamurthy, R Kulkarni, N Bottini, AM Barrios J. Med. Chem. 2009, 52, 6912-6918. Published, 2009.
  • Profiling Protein Tyrosine Phosphatase Activity with Chemical Probes D Krishnamurthy, AM Barrios Curr. Opin. Chem. Biol. 2009, 13, 375-381. Published, 2009.
  • “Identifying Selective Protein Tyrosine Phosphatase Substrates and Inhibitors from a Fluorogenic, Combinatorial Peptide Library” S. Mitra and A. M. Barrios, ChemBioChem 2008, 9(8), 1216-1219. Published, 2008.
  • “Inhibition of Cathepsin B by Au(I) Complexes: A Kinetic and Computational Study” S. S. Gunatilleke, C. A. F. de Oliviera, J. A. McCammon and A. M. Barrios, J. Med. Chem. 2008, 13(4), 555-561. Published, 2008.
  • “Tuning the Au(I)-Mediated Inhibition of Cathepsin B Through Ligand Substitutions” S. S. Gunatilleke and A. M. Barrios J. Inorg. Biochem. 2008, 102, 555-563 (special issue dedicated to CanBIC). Published, 2008.
  • “A Highly Efficient Route to Enantiomerically Pure l-N-Bz-Pmp(t-Bu)2-OH and Incorporation into a Peptide-Based Protein Tyrosine Phosphatase Inhibitor” C. E. Hubbard and A. M. Barrios, Bioorg. Med. Chem. Lett. 2008 18, 679-681. Published, 2008.
  • “Spectroscopic Evidence for the Formation of Goldfingers” M. A. Franzman and A. M. Barrios, Inorg. Chem. 2008 47, 3928-3930. Published, 2008.
  • “Gold(I)-Mediated Inhibition of Protein Tyrosine Phosphatases” D. Krishnamurthy, M. R. Karver, E. Fiorillo, V. Orru, S. M. Stanford, N. Bottini and A. M. Barrios, J Med. Chem. 2008, 51, 4790-4795. Published, 2008.
  • “Identifying and Characterizing the Biological Targets of Metallotherapeutics: Two approaches using Au(I)-protein interactions as model systems” M. R. Karver and A. M. Barrios, Anal. Biochem. 2008 382, 63-65. Published, 2008.