Ryan E. Looper

ORGANIC & BIOORGANIC CHEMISTRY

Henry Eyring Associate Professor

B.S. Western Washington University, 1998
M.Sc. Western Washington University, 1999
Ph.D. Colorado State University, 2004
NIH Postdoctoral Fellow Harvard University, 2004-2007

 

Phone: (801) 585-0408

Office: 3166 HEB-N

Email: r.looper@utah.edu

Research Group

Biological Chemistry Program

Activities & Awards

  • Entrepreneurial Faculty Scholar, University of Utah, 2014
  • Eli Lilly Young Investigator Award, 2013
  • Amgen Young Investigator Award, 2012
  • Thieme Chemistry Journal Award, 2012
  • Henry Eyring Assistant Professor of Chemistry, 2009
  • NIH Ruth L. Kirschstein National Research Service Award, 2005
  • Array Biopharma Research Fellowship, 2003
  • Western Assoc. of Graduate Schools/UMI Distinguished Thesis Award, 2001

Research Interests

Our research program focuses on the behavior of small molecules within biological systems. With clues from nature, we aim to develop compounds as specific modulators of cell signaling events and as tools for a community.

Initially, our synthetic achievements will support the exploration of post-translational protein-arginine modifications and its consequences. The recent implication of these events in a number of disease states (multiple sclerosis, rheumatoid arthritis, glaucoma and tumorogenesis) encourages the preparation of biological tools and therapeutic leads.

Insight into the mechanism of action of natural products will inspire the development of new synthetic methodology and fragment based small molecule collections. In part, these advances will access natural product families which exhibit a wide range of biological activities. The efficient construction of these skeletons will allow us to investigate the evolutionary conservation of their biosynthesis by their contribution to the national screening infrastructure.

We are also developing antibiotic collections for the inhibition of prokaryotic protein synthesis. Molecules with purported rRNA binding interactions that are uncharacterized or non-overlapping with known sites of resistance will be targeted to advance our understanding of RNA’s binding topology.

Selected Publications

  • Ki-hyeok Kwon, Catherine M. Serrano, Michael Koch, Louis R. Barrows and Ryan E. Looper "Synthesis of bicyclic guanidines via cascade hydroamination /Michael additions of mono-N-acylpropargylguanidines" Organic Letters 2014, in press. 
  • Jing Fan, Xin Teng, Ling Liu, Katherine R. Mattaini, Ryan E. Looper, Matthew G. Vander Heiden and Joshua D. Rabinowitz "Human phosphoglycerate dehydrogenase produces the oncometabolite D-2-hydroxyglutarate" ACS Chemical Biology 2014, in press.
  • Kaitlin J. Basham, Christopher J. Leonard, Collin Kieffer, Dawne N. Shelton, Maria E. McDowell, Vasudev R. Bhonde, Ryan E. Looper, and Bryan E. Welm "Dioxin Exposure Blocks Lactation Through a Driect Effect on Mammary Epithelial Cells Mediated by the Aryl Hydrocarbon Receptor Repressor" Toxicol. Sci. 2014, in press.
  • Kaitlin J. Basham, Vasudev R. Bhonde, Collin Keiffer, James B. C. Mack, Matthew Hess, Bryan E.  Welm and Ryan E. Looper* “ Bis-aryloxadiazoles as effective activators of the aromatic hydrocarbon receptor” Bioorg. Med. Chem. Lett.2014, 24, 2473-2476.  DOI: 10.1016/j.bmcl.2014.04.013. 
  • Kihyeok Kwon, Travis J. Haussener and Ryan E. Looper* "Preparation of mono-Cbz protected guanidines (Potassium carbobenzyloxycyanamide, carbobezyloxycyanamide potassium salt)" 2014, Organic Synthesis (in revision).
  • Keith M. Gligorich, Rachel M. Vaden, Dawne N. Shelton, Guoying Wang, Cindy B. Matsen, Ryan   E. Looper, Matthew S. Sigman, and Bryan E. Welm “Development of a Screen To Identify     Selective Small Molecules Active Against Patient-Derived Metastatic and Chemoresistant Breast Cancer Cells”  Breast Cancer Research, 201315(4), R58. PMID: 23879992. PMC4028696. 
  • Miao Yang, Shannon Odelberg, Dean Li and Ryan E. Looper* “Cationic-Rh(II) complexes for the synthesis of dihydropyrimidines from propargylureas”2013, Tetrahedron, 69, 5744-5750. DOI:10.1016/j.tet.2013.04.071.
  • Vasudev R. Bhonde and Ryan E. Looper* "Carbamic acid, N-[[[(1,1 dimethylethoxy)carbonyl]amino](methylthio)methylene]-,11-dimethylethyl ester" Encyclopedia of Reagents for Organic Synthesis (eROS), 2013, in press. DOI: 10.1002/047084289X.rn01529
  • Julie-Aurore Losman, Ryan Looper, Peppi Koivunen, Sungwoo Lee, Rebekka K. Schneider, Christine McMahon, Glenn Cowley, David Root, Benjamin L. Ebert, and William G. Kaelin Jr. “(R)-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible” Science, 2013, 339, 1621-1625. DOI:10.1126/science.1231677
  • Kaitlin J. Basham, Collin Keiffer, Dawne  N. Shelton, Chris J. Leonard, Vasudev R. Bhonde, Hariprasad Vankayalapati, Brett Milash, David J. Bearss , Ryan E. Looper and Bryan E. Welm “Chemical genetic screen reveals a role for desmosomal adhesion in mammary branching morphogenesis.” J. Biol. Chem. 2013, 288(4), 2261-2270.
  • Joseph B. Gibbons, Keith M. Gligorich, Bryan E. Welm and Ryan E. Looper* “Synthesis of the reported structures for kealiinines B and C” Organic Letters 2012, 14, 4734-4737. DOI: 10.1021/ol3019242
  • T. J. Haussener and R, E. Looper “An epoxide opening cascade to access the pactamycin core” Org. Lett.2012, in press.
  • V. R. Bhonde and R. E. Looper “Carbamic acid, N-[[[(1,1 dimethylethoxy)carbonyl] amino](methylthio)methylene]-,1,1-dimethylethyl ester” Encyclopedia of Reagents for Organic Synthesis (eROS), 2012, in press.
  • R. E. Looper and R. M. Williams “Efficient Asymmetric Synthesis of N-tert-Butoxycarbonyl-alpha-Aminoacids using 4-tert-Butoxycarbonyl-5,6-Diphenylmorpholin-2-one: (R)-(N-tert-Butoxycarbonyl)allylglycine” Org. Syn. 2012, 89, 394-403.
  • P. Koivunen, S. Lee, C. G. Duncan, G. Lopez, S. Ramkissoon, J. Losman, P. Joensuu, U. Bergmann, S. Gross, R. Looper, K. Ligon, R. Verhaak, H. Yan, and W. G. Kaelin, Jr. “Transformation by the (R) Enantiomer of 2-Hydroxyglutarate Linked to EglN Activation.” Nature2012, 483, 484-488.
  • V. R. Bhonde and R. E. Looper “A stereocontrolled synthesis of (+)-saxitoxin” J. Am. Chem. Soc. 2011, 133, 20172-20174.
  • C. M. Serrano and R. E. Looper “Rapid assembly of cytimidine through tandem Cu-catalyzed N-aryl amidation reactions” Org. Lett.2011, 13, 5000-5003.
  • R. E. Looper, T. J. Haussener and J. B. C. Mack “Chlorotrimethylsilane activation of acylcyanamides for the synthesis of mono-N-acylguanidines” J. Org. Chem.2011, 76, 6967-6971.
  • M. J. Gainer, N. R. Bennett, Y. Takahashi and R. E. Looper “Regioselective Rh(II)-catalyzed hydroaminations of propargylguanidines” Angew. Chem. Int. Ed.2011, 50, 684-687.
  • R. L. Giles, R. A. Nkansah and R. E. Looper “Synthesis of 2-thio and 2-oxoimidazoles via cascade addition-cycloisomerization reactions of propargylcyanamides” J. Org. Chem.2010, 75, 261-264.
  • M. R. Kaadige, R. E. Looper, Ka. Sadhaasivam and D. E. Ayer “Glutamine-dependent anapleurosis dictates glucose uptake and cell growth by regulating MondoA transcriptional activity" Proc. Nat. Acad. Sci. USA 2009, 106, 14878-14883.
  • R. L. Giles, J. D. Sullivan, A. M. Steiner and R. E. Looper “Addition-hydroamination reactions of propargyl cyanamides: Rapid access to highly substituted 2-aminoimidazoles " Angew. Chem. Int. Ed.2009, 48, 3116-3120.
  • J. D. Sullivan, R. L. Giles and R. E. Looper “2-aminoimidazoles from Leucetta sponges: synthesis and biology of an important pharmacophore" Curr. Bioactive Cmpds. 2009, 5, 39-78.
  • R. E. Looper, D. Pizzirani, S.L. Schreiber “Macrocycloadditions leading to conformationally restricted small molecules” Org. Lett.2006, 8, 2063-2066.

  • R. E. Looper, M. T. C. Runnegar, R. M. Williams“Syntheses of the cylindrospermopsin alkaloids and their toxicological evaluationTetrahedron2006, 62, 4549–4562.

  • R. E. Looper, M. T.C. Runnegar, R. M. Williams“Synthesis of the putative structure of 7-deoxycylindrospermopsin: C7-oxygenation is not required for the inhibition of protein synthesis” Angew. Chem. Int. Ed.2005, 44, 3879-3881.

  • R. E. Looper and R. M. Williams “A concise asymmetric synthesis of the marine hepatotoxin 7-epi-cylindrospermopsin” Angew. Chem. Int. Ed.2004, 43, 2930-2933.(VIP paper)

  • R. E. Looper and R. M. Williams “Construction of cylindrospermopsin’s A ring via an intramolecular oxazinone-N-oxide dipolar cycloaddition” Tetrahedron Lett.2001, 42, 769-771.

  • J. R. Vyvyan, C. Loitz, R. E. Looper, C. S. Mattingly, E. A. Peterson, S. T. Staben “Synthesis of aromatic bisabolene natural products via palladium-catalyzed cross couplings of organozinc reagents” J. Org. Chem. 2004, 69, 2461-2468.