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Amy Barrios

Associate Professor of Medicinal Chemistry

Amy Barrios

B.S. University of Utah

Ph.D. Massachusetts Institute of Technology

Research

References

amy.barrios@utah.edu

Amy Barrios' Lab Page

Amy Barrios' PubMed Literature Search

Biological Chemistry Program

Metals in Medicine, Probes of Tyrosine Phosphorylation, Functional Profiling of the Microbiome

Research

Despite the therapeutic relevance of many human PTPs, our understanding of their biological substrates, substrate selectivity, cellular regulation and druggability is limited. Research in the Barrios lab focuses on addressing these challenges through the development and application of novel chemical probes, specifically 1) using fluorogenic probes to investigate PTP activity and regulation during cellular signaling, 2) profiling the substrate selectivities of the PTP family of enzymes and 3) utilizing PTP substrate selectivity profiles in the design of potent, selective inhibitors and probes. We are particularly interested in PTPs involved in human autoimmunity and T-cell receptor signaling.

Our laboratory also has an interest in using chemical tools to study the therapeutic roles of metal ions and understanding the functional contributions of the gut microbiome to xenobiotic and nutrient metabolism. In particular, we have had a longstanding interest in the biological targets of gold-based antiarthritic compounds and are actively involved in collaborative work aimed at repurposing these drugs for new applications including parasite infections and inflammation. We have recently become interested in the human microbiome and are working to develop a platform technology capable of identifying the principle enzyme activities present in a complex microbial sample with the long-term goal of developing a detailed understanding  of the roles that bacteria play in xenobiotic and nutrient metabolism.

References

  1. “Lanthanide complexes as luminogenic probes to measure sulfide levels in industrial samples” M. K. Thorson, P. Ung, F. M. Leaver, T. S. Corbin, K. L. Tuck*, B. Graham*, A. M. Barrios*. Anal. Chim. Acta2015, 896, 160-165.
  2. “Marine Natural Products as Inhibitors of Cystathionine beta-Synthase Activity” M. K. Thorson, R. M. Van Wagoner, M. K. Harper, C. M. Ireland, T. Majtan, J. P. Kraus, A. M. Barrios. Bioorg. Med. Chem. Lett.2015, 25, 1064-1066.
  3. “Early Endosomal Escape of a Cyclic Cell-Penetrating Peptide Enables Effective Cytosolic Cargo Delivery” Z. Qian, J. LaRochelle, B. Jiang, W. Lian, R. Hard, N. G. Selner, R. Leuchapanichkul, A. M. Barrios, D. Pei. Biochem. 2014, 53(24), 4034-4046.
  4. “Inhibition of the Lymphoid Tyrosine Phosphatase: The Effect of Zinc(II) ions and Chelating Ligand Fragments on Enzymatic Activity” M. K. Thorson, D. T. Puerta, S. M. Cohen, A. M. Barrios. Bioorg. Med. Chem. Lett.2014,24(16), 4019-4022.
  5. “Auranofin is an Apoptosis Stimulating Agent with in vitro and in vivo Anti-Leishmanial Activity” E. Sharlow, S. Leimgruber, S. Murray, A. Lira, R. Sciotti, M. Hickman, T. Hudson, S. Leed, D. Caridha, A. M. Barrios, D. Close, M. Grogl, J. Lazo. ACS Chem. Biol.2014, 9(3), 663-672.
  6. “Monitoring Intracellular Protein Tyrosine Phosphatase Activity” S. M. Stanford, V. F. Ahmed, N. Bottini, A. M. Barrios. Antioxidants and Redox Signaling 2014, 20(14), 2160-2178.
  7. “Covalent Inhibition of the Lymphoid Tyrosine Phosphatase” V. F. Ahmed, N. Bottini & A. M. BarriosChemMedChem2014, 9(2), 296-299.
  8. “pCAP-Based Peptide Substrates: The New Tool in the Box of Tyrosine Phosphatase Assays” S. M. Stanford, D. Krishnamurthy, C. E. Karver, E. Bruenger, L. Walker, C.-T. Ma, T. D. Y. Chung, E. Sergienko, N. Bottini, A. M. Barrios. Methods 2014, 65, 165-174.
  9. “Substrate Selection Influences Molecular Recognition in a Screen for Lymphoid Tyrosine Phosphatase Inhibitors” R. A. Kulkarni, N. A. Vellore, M. R. Bliss, S. M. Stanford, M. D. Falk, N. Bottini, R. Baron, A. M. Barrios. ChemBioChem 2013,14(13), 1640-1647.
  10. “Thiuram Disulfides as Irreversible Inhibitors of the Lymphoid Tyrosine Phosphatase” R. A. Kulkarni, S. M. Stanford, N. A. Vellore, M. R. Bliss, D. Krishnamurthy, R. Baron, N. Bottini, A. M. Barrios. ChemMedChem 2013, 8(9), 1561-1568.
  11. “Medicinal Inorganic Chemistry: a web themed issue” A. M. Barrios, S. M. Cohen, M. H. Lim. Chem. Commun.2013, 49, 5910-5911.
  12. “A Potent and Selective Small Molecular Inhibitor for the Lymphocyte-Specific Tyrosine Phosphatase (LYP), a Common Risk Factor Associated with Autoimmune Diseases” Y. He, S. Liu, A. Menon, S. M. Stanford, E. Oppong, A. M. Gunawan, L. Wu, A. M. Barrios, N. Bottini, A. C. B. Cato, Z.-Y. Zhang. J. Med. Chem, 2013, 56(12) 4990-5008.
  13. “Identification of Cystathionine beta-Synthase Inhibitors Using a Novel Hydrogen Sulfide Selective Probe” M. K. Thorson, T. Majtan, J. P. Kraus, A. M. Barrios.Angew. Chem. 2013, 52, 4641-4644.
  14. “Efficient Delivery of Cyclic Peptides into Mammalian Cells with Short Sequence Motifs” Z. Qian, T. Liu, Y.-Y. Liu, R. Briesewitz, A. M. Barrios, S. M. Jhiang, D. Pei. ACS Chem. Biol.2013,8(2), 423-431.
  15. “High-Throughput Screen Using a Single-Cell Tyrosine Phosphatase Assay Reveals Biologically Active CD45 Inhibitors” S. M. Stanford, R. G. Panchal, L. M. Walker, M. D. Falk, S. Mitra, S. S. Damle, D. Ruble, T. Kaltcheva, S. Zhang, Z.-Y. Zhang, S. Bavari, A. M. Barrios, N. Bottini. Proc. Natl. Acad. Sci.2012, 109(35), 13972-13977.
  16. “A High-Throughput Drug Screen for Entamoeba histolytica identifies a new lead and target” A. Debnath, D. Parsonage, R. Andrade, C. He, E. Cobo, K. Hirata, S. Chen, G. Garcia-Rivera, E. Orozco, M. Martinez, S. Gunatilleke, A. M. Barrios, M. Arkin, L. Poole, J. McKerrow, S. Reed. Nat. Med.2012, 18(6), 956-960.
  17. “PEST-Domain-Enriched Tyrosine Phosphatase and Glucocorticoids as Regulators of Anaphylaxis in Mice.” D. Obiri, N. Flink, J. Maier, A. Neeb, D. Maddalo, W. Thiele, A. Menon, M. Stasson, R. Kulkarni, M. Garabedian, A. M. Barrios, A. Cato. Allergy2012, 67, 175-182.
  18. “Discovery of a Novel Series of Inhibitors of Lymphoid Tyrosine Phosphatase with Activity in Human T Cells” S. Stanford, D. Krishnamurthy, M. Falk, R. Messina, B. Debnath, S. Li, T. Liu, R. Kazemi, R. Dahl, Y. He, X. Yu, A. Chan, Z.-Y. Zhang, A. M. Barrios, V. Woods, N. Neamati, N. Bottini. J. Med. Chem. 2011, 54, 1640-1654.
  19. “Oxidative Inactivation of the Lymphoid Tyrosine Phosphatase Mediated by Both General and Active Site Directed NO Donors” C. E. Karver, V. F. Ahmed and A. M. Barrios.Bioorg. Med. Chem. Lett. 2011, 21, 285-287.
  20. “Gold(I) Phosphine-Mediated, Selective Inhibition of Lymphoid Tyrosine Phosphatase” M. R. Karver, D. Krishnamurthy, N. Bottini and A. M. BarriosJ. Inorg. Biochem. 2010, 104(3) 268-273.
  21. “Identifying Potent, Selective Protein Tyrosine Phosphatase Inhibitors from a Library of Au(I) Complexes” M. R. Karver, D. Krishnamurthy, R. Kulkarni, N. Bottini and A. M. Barrios.J. Med. Chem. 2009, 52, 6912-6918.
  22. “Profiling Protein Tyrosine Phosphatase Activity with Chemical Probes” D. Krishnamurthy and A. M. BarriosCurr. Opin. Chem. Biol.2009,13, 375-381 (invited review).
  23. “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.
  24. “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.
  25. “Spectroscopic Evidence for the Formation of Goldfingers” M. A. Franzman and A. M. Barrios. Inorg. Chem. 2008, 47, 3928-3930.
  26. “Identifying Selective Protein Tyrosine Phosphatase Substrates and Inhibitors from a Fluorogenic, Combinatorial Peptide Library” S. Mitra and A. M. Barrios. ChemBioChem2008, 9(8), 1216-1219.
  27. “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. Biol. Inorg. Chem.2008, 13(4), 555-561.
  28. “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).
  29. “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.
  30. “A Series of Peptide-Based, Fluorogenic Probes for Protein Tyrosine Phosphatase Activity” S. Mitra and A. M. Barrios.Anal. Biochem.2007, 370, 249-251.
  31. “Inhibition of Lysosomal Cysteine Proteases by Au(I) Compounds: A Detailed Mechanistic Investigation” S. S. Gunatilleke and A. M. Barrios. J. Med. Chem. 2006, 49(13), 3933-3937.
  32. “Intracellular Metal Detectors” A. M. Barrios. ACS Chem. Biol. 2006, 1(2), 67-68.
  33. “Highly Sensitive Peptide-Based Probes for Protein Tyrosine Phosphatase Activity Utilizing a Fluorogenic Mimic of Phosphotyrosine” S. Mitra and A. M. Barrios.Bioorg. Med. Chem. Lett.2005, 15, 5142-5145.
  34. “Inhibition of Lysosomal Cysteine Proteases by Chrysotherapeutic Compounds: A Possible Mechanism for the Antiarthritic Activity of Au(I).” A. Chircorian and A. M. Barrios.Bioorg. Med. Chem. Lett. 2004, 14, 5113-5116.

RESEARCH: Publications from work prior to becoming an Assistant Professor:.

  1. “Scanning the Prime-Site Substrate Specificity of Proteolytic Enzymes: A Novel Assay Based on Ligand-Enhanced Lanthanide Ion Fluorescence." A. M. Barrios and C. S. Craik. Bioorg. Med. Chem. Lett.2002, 12, 3619-3623.
  2. “Decomposition of Alkyl-Substituted Urea Molecules at a Hydroxide-Bridged Dinickel Center." A. M. Barrios and S. J. Lippard. Inorg. Chem.2001, 40, 1250-1255.
  3. “Phthalazine-Based Dinucleating Ligands Afford Dinuclear Centers Often Encountered in Metalloenzyme Active Sites." A. M. Barrios and S. J. Lippard. Inorg. Chem. 2001, 40, 1060-1064.
  4. “Diiron Complexes of 1,8-Naphthyridine-Based Dinucleating Ligands as Models for Hemerythrin." C. He, A. M. Barrios, D. Lee, J. Kuzelka, R. M. Davydov and S. J. Lippard. J. Am. Chem. Soc. 2000, 122, 12683-12690.
  5. “Interaction of Urea with a Hydroxide-Bridged Dinuclear Nickel Center: An Alternative Model for the Mechanism of Urease." A. M. Barrios and S. J. Lippard. J. Am. Chem. Soc. 2000, 122, 9172-9177.
  6. “Amide Hydrolysis Effected by a Hydroxo-Bridged Dinickel(II) Complex: Insights into the Mechanism of Urease." A. M. Barrios and S. J. Lippard. J. Am. Chem. Soc.1999, 121, 11751-11757.
  7. “The Reactivity of Well Defined Diiron(III) Peroxo Complexes Toward Substrates: Addition to Electrophiles and Hydrocarbon Oxidation." D. D. LeCloux, A. M. Barrios and S. J. Lippard. Bioorg. Med. Chem.1999, 7, 763-772.
  8. “Modeling the Diiron Centers of Non-Heme Iron Enzymes. Preparation of Sterically Hindered Diiron(II) Tetracarboxylate Complexes and Their Reactions with Dioxygen." D. D. LeCloux, A. M. Barrios, T. J. Mizoguchi and S. J. Lippard. J. Am. Chem. Soc.1998, 120, 9001-9014.
  9. “Synthesis of 2-Alkyl-3-Hydroxy-4-Pyridinone-Ribonucleosides, Potential Oral Iron Chelators." G. Liu, F. W. Bruenger, A. M. Barrios, S. C. Miller. Nucleosides and Nucleotides1995, 14, 1901-1904.

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Last Updated: 8/19/17