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Amy Barrios

Professor of Medicinal Chemistry

Associate Dean of Postdoc Affairs

Protein Phosphorylation, Chemical Probe Development, Metals in Medicine

Amy Barrios

 

Biological Chemistry Program

Education

B.S. University of Utah

Ph.D. Massachusetts Institute of Technology

 

 

Research

Despite the therapeutic relevance of many human protein phosphatases, 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 protein phosphatase activity and regulation during cellular signaling, 2) investigating the impact of protein phosphorylation on structure and function and 3) identifying protein phosphatase inhibitors for use as therapeutic lead compounds. We are particularly interested in protein phosphatases involved in immune system dysregulation, cancer, and neurological disease. 

References

  1. “PTPs: Degrading the Undruggable” A. M. BarriosJ. Med. Chem. 2020, 63(14), 7508-7509.
  2. “Fluorogenic Probes for Imaging Cellular Phosphatase Activity” B. S. McCullough and A. M. BarriosCurr. Opin. Chem. Biol.2020, 57, 34-40.
  3. “In vitro Assays for Measuring Protein Histidine Phosphatase Activity” B. S. McCullough and A. M. BarriosIn Histidine Phosphorylation Methods and Protocols; C. E. Eyers, Ed.; Methods in Molecular Biology 2077; Humana Press: New York, NY, 2020; 109-120. 
  4. “Synthesis and PTP inhibitory activity of illudalic acid and its methyl ether, with insights into selectivity for LAR PTP over other tyrosine phosphatases under physiologically relevant conditions” B. S. McCullough, P. Batsomboon, K. B. Hutchinson, G. B. Dudley and A. M. BarriosJ. Nat. Prod. 201982, 3386-3393.
  5. “Rational design of a SHP-2 targeted, fluorogenic peptide substrate” E. S. Ma and A. M. BarriosBioorg. Med. Chem. Lett.201929(17), 2452-2454.
  6. "In Vitro Assays for Measuring Protein Histidine Phosphatase Activity." McCullough and A. M. Barrios Methods Mol Biol.2020 2077:109-120. doi: 10.1007/978-1-4939-9884-5_8.
  7. “Facile, Fluorogenic Assay for Protein Histidine Phosphatase Activity” B. S. McCullough and A. M. BarriosBiochem.2018 57(18), 2584-2589.
  8. “A luminogenic lanthanide-based probe for the highly selective detection of nanomolar sulfide levels in aqueous samples” M. L. Aulsebrook, S. Biswas, F. M. Leaver, M. R. Grace, B. Graham, A. M. Barrios, K. L. Tuck Chem. Commun.2017, 53, 4911-4914.
  9. “Dual Colorimetric and Fluorogenic Probes for Visualizing Tyrosine Phosphatase Activity and High Throughput Screening” S. Biswas, B. S. McCullough, C. W. Russell, D. G. Brown, J. L. Round, M. A. Mulvey, A. M. BarriosChem. Commun. 2017, 53, 2233-2236.
  10. “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.
  11. “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.
  12. “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.
  13. “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.
  14. “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.
  15. “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.
  16. “Covalent Inhibition of the Lymphoid Tyrosine Phosphatase” V. F. Ahmed, N. Bottini & A. M. BarriosChemMedChem2014, 9(2), 296-299.
  17. “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.
  18. “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.
  19. “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.
  20. “Medicinal Inorganic Chemistry: a web themed issue” A. M. Barrios, S. M. Cohen, M. H. Lim. Chem. Commun.2013, 49, 5910-5911.
  21. “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.
  22. “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.
  23. “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.
  24. “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.
  25. “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.
  26. “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.
  27. “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.
  28. “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.
  29. “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.
  30. “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.
  31. “Profiling Protein Tyrosine Phosphatase Activity with Chemical Probes” D. Krishnamurthy and A. M. BarriosCurr. Opin. Chem. Biol.2009,13, 375-381 (invited review).
  32. “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.
  33. “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.
  34. “Spectroscopic Evidence for the Formation of Goldfingers” M. A. Franzman and A. M. Barrios. Inorg. Chem. 2008, 47, 3928-3930.
  35. “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.
  36. “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.
  37. “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).
  38. “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.
  39. “A Series of Peptide-Based, Fluorogenic Probes for Protein Tyrosine Phosphatase Activity” S. Mitra and A. M. Barrios.Anal. Biochem.2007, 370, 249-251.
  40. “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.
  41. “Intracellular Metal Detectors” A. M. Barrios. ACS Chem. Biol. 2006, 1(2), 67-68.
  42. “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.
  43. “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.

 

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.
Last Updated: 9/7/21