Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation

Smith, Thomas P.; Windsor, Ian W.; Forest, Katrina T.; Raines, Ronald T.

doi:10.1021/acs.jmedchem.7b00952

Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation

Journal Article · Mon Sep 18 00:00:00 EDT 2017 · Journal of Medicinal Chemistry

DOI:https://doi.org/10.1021/acs.jmedchem.7b00952· OSTI ID:1438876

Smith, Thomas P. ^[1]; Windsor, Ian W. ^[1]; Forest, Katrina T. ^[1]; ^[1]

Univ. of Wisconsin, Madison, WI (United States)

Transthyretin (TTR) is a homotetrameric protein. Its dissociation into monomers leads to the formation of fibrils that underlie human amyloidogenic diseases. The binding of small molecules to the thyroxin-binding sites in TTR stabilizes the homotetramer and attenuates TTR amyloidosis. Herein, we report on boronic acid-substituted stilbenes that limit TTR amyloidosis in vitro. Assays of affinity for TTR and inhibition of its tendency to form fibrils were coupled with X-ray crystallographic analysis of nine TTR·ligand complexes. The ensuing structure–function data led to a symmetrical diboronic acid that forms a boronic ester reversibly with serine 117. This diboronic acid inhibits fibril formation by both wild-type TTR and a common disease-related variant, V30M TTR, as effectively as does tafamidis, a small-molecule drug used to treat TTR-related amyloidosis in the clinic. We conclude these findings establish a new modality for covalent inhibition of fibril formation and illuminate a path for future optimization.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Genentech Predoctoral Fellowship; National Institutes of Health (NIH); National Science Foundation (NSF)

OSTI ID:: 1438876

Journal Information:: Journal of Medicinal Chemistry, Journal Name: Journal of Medicinal Chemistry Journal Issue: 18 Vol. 60; ISSN 0022-2623

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (77)

Molecular recognition with boronic acids—applications in chemical biology Whyte, Gillian F.; Vilar, Ramon; Woscholski, Rudiger Journal of Chemical Biology, Vol. 6, Issue 4 https://doi.org/10.1007/s12154-013-0099-0	journal	June 2013
n-Alkylboronic acids as bifunctional reversible inhibitors of α-chymotrypsin Antonov, V. K.; Ivanina, T. V. FEBS Letters, Vol. 7, Issue 1 https://doi.org/10.1016/0014-5793(70)80607-x	journal	March 1970
Crystal Structure of the Boronic Acid-Based Proteasome Inhibitor Bortezomib in Complex with the Yeast 20S Proteasome Groll, Michael; Berkers, Celia R.; Ploegh, Hidde L. Structure, Vol. 14, Issue 3 https://doi.org/10.1016/j.str.2005.11.019	journal	March 2006
Transthyretin mutation Leu-55-Pro significantly alters tetramer stability and increases amyloidogenicity McCutchen, Sandra L.; Colon, Wilfredo; Kelly, Jeffery W. Biochemistry, Vol. 32, Issue 45 https://doi.org/10.1021/bi00096a024	journal	November 1993
Structural analysis of specificity: .alpha.-lytic protease complexes with analogs of reaction intermediates Bone, Roger; Frank, Dan; Kettner, Charles A. Biochemistry, Vol. 28, Issue 19 https://doi.org/10.1021/bi00445a015	journal	September 1989
2-Phenylethaneboronic acid, a possible transition-state analog for chymotrypsin Lienhard, Gustav E.; Koehler, Karl A. Biochemistry, Vol. 10, Issue 13 https://doi.org/10.1021/bi00789a008	journal	June 1971
Boron Containing Compounds as Protease Inhibitors Smoum, Reem; Rubinstein, Abraham; Dembitsky, Valery M. Chemical Reviews, Vol. 112, Issue 7 https://doi.org/10.1021/cr608202m	journal	April 2012
Boronate-Mediated Biologic Delivery Ellis, Gregory A.; Palte, Michael J.; Raines, Ronald T. Journal of the American Chemical Society, Vol. 134, Issue 8 https://doi.org/10.1021/ja210719s	journal	February 2012
Aromatic Sulfonyl Fluorides Covalently Kinetically Stabilize Transthyretin to Prevent Amyloidogenesis while Affording a Fluorescent Conjugate Grimster, Neil P.; Connelly, Stephen; Baranczak, Aleksandra Journal of the American Chemical Society, Vol. 135, Issue 15 https://doi.org/10.1021/ja311729d	journal	February 2013
A Fluorogenic Aryl Fluorosulfate for Intraorganellar Transthyretin Imaging in Living Cells and in Caenorhabditis elegans Baranczak, Aleksandra; Liu, Yu; Connelly, Stephen Journal of the American Chemical Society, Vol. 137, Issue 23 https://doi.org/10.1021/jacs.5b03042	journal	June 2015
Synthesis, Structure, and Activity of Diclofenac Analogues as Transthyretin Amyloid Fibril Formation Inhibitors Oza, Vibha B.; Smith, Craig; Raman, Prakash Journal of Medicinal Chemistry, Vol. 45, Issue 2 https://doi.org/10.1021/jm010257n	journal	December 2001
Diflunisal Analogues Stabilize the Native State of Transthyretin. Potent Inhibition of Amyloidogenesis Adamski-Werner, Sara L.; Palaninathan, Satheesh K.; Sacchettini, James C. Journal of Medicinal Chemistry, Vol. 47, Issue 2 https://doi.org/10.1021/jm030347n	journal	January 2004
Ligand-promoted protein folding by biased kinetic partitioning Hingorani, Karan S.; Metcalf, Matthew C.; Deming, Derrick T. Nature Chemical Biology, Vol. 13, Issue 4 https://doi.org/10.1038/nchembio.2303	journal	February 2017
Fluorogenic Assay for Inhibitors of HIV-1 Protease with Sub-picomolar Affinity Windsor, Ian W.; Raines, Ronald T. Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep11286	journal	August 2015
Boronic acids in medicinal chemistry: anticancer, antibacterial and antiviral applications Trippier, Paul C.; McGuigan, Christopher MedChemComm, Vol. 1, Issue 3 https://doi.org/10.1039/c0md00119h	journal	January 2010
Inhibiting transthyretin amyloid fibril formation via protein stabilization Miroy, G. J.; Lai, Z.; Lashuel, H. A. Proceedings of the National Academy of Sciences, Vol. 93, Issue 26 https://doi.org/10.1073/pnas.93.26.15051	journal	December 1996
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/s0907444910007493	journal	March 2010
Recent progress in the understanding and treatment of transthyretin amyloidosis Sekijima, Y. Journal of Clinical Pharmacy and Therapeutics, Vol. 39, Issue 3 https://doi.org/10.1111/jcpt.12145	journal	April 2014
Sulfated Metabolites of Polychlorinated Biphenyls Are High-Affinity Ligands for the Thyroid Hormone Transport Protein Transthyretin Grimm, Fabian A.; Lehmler, Hans-Joachim; He, Xianran Environmental Health Perspectives, Vol. 121, Issue 6 https://doi.org/10.1289/ehp.1206198	journal	June 2013
Novel Transthyretin Amyloid Fibril Formation Inhibitors: Synthesis, Biological Evaluation, and X-Ray Structural Analysis Palaninathan, Satheesh K.; Mohamedmohaideen, Nilofar N.; Orlandini, Elisabetta PLoS ONE, Vol. 4, Issue 7 https://doi.org/10.1371/journal.pone.0006290	journal	July 2009
Familial amyloidotic polyneuropathy: current and emerging treatment options for transthyretin-mediated amyloidosis Hund, Ernst The Application of Clinical Genetics https://doi.org/10.2147/tacg.s19903	journal	June 2012
Targeted Covalent Inhibitors for Drug Design Baillie, Thomas A. Angewandte Chemie International Edition, Vol. 55, Issue 43 https://doi.org/10.1002/anie.201601091	journal	August 2016
A Boronic Acid Conjugate of Angiogenin that Shows ROS-Responsive Neuroprotective Activity Hoang, Trish T.; Smith, Thomas P.; Raines, Ronald T. Angewandte Chemie International Edition, Vol. 56, Issue 10 https://doi.org/10.1002/anie.201611446	journal	January 2017
Reversible Lysine Modification on Proteins by Using Functionalized Boronic Acids Cal, Pedro M. S. D.; Frade, Raquel F. M.; Cordeiro, Carlos Chemistry - A European Journal, Vol. 21, Issue 22 https://doi.org/10.1002/chem.201500127	journal	April 2015
Ligand binding to proteins: The binding landscape model Miller, David W.; Dill, Ken A. Protein Science, Vol. 6, Issue 10 https://doi.org/10.1002/pro.5560061011	journal	October 1997
Transthyretin: a review from a structural perspective Hamilton, J. A.; Benson, M. D. Cellular and Molecular Life Sciences, Vol. 58, Issue 10 https://doi.org/10.1007/PL00000791	journal	September 2001
Tafamidis: A Review of Its Use in Familial Amyloid Polyneuropathy Scott, Lesley J. Drugs, Vol. 74, Issue 12 https://doi.org/10.1007/s40265-014-0260-2	journal	July 2014
n-Alkylboronic acids as bifunctional reversible inhibitors of α-chymotrypsin Antonov, V. K.; Ivanina, T. V. FEBS Letters, Vol. 7, Issue 1 https://doi.org/10.1016/0014-5793(70)80607-X	journal	March 1970
Inhibition of the serine proteases leukocyte elastase, pancreatic elastase, cathepsin G, and chymotrypsin by peptide boronic acids. Kettner, C. A.; Shenvi, A. B. Journal of Biological Chemistry, Vol. 259, Issue 24 https://doi.org/10.1016/S0021-9258(17)42521-X	journal	December 1984
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Assessing the (a)symmetry of concentration-effect curves Giraldo, Jesús; Vivas, Nuria M.; Vila, Elisabet Pharmacology & Therapeutics, Vol. 95, Issue 1 https://doi.org/10.1016/S0163-7258(02)00223-1	journal	July 2002
Discovering transthyretin amyloid fibril inhibitors by limited screening Baures, Paul W.; Peterson, Scott A.; Kelly, Jeffery W. Bioorganic & Medicinal Chemistry, Vol. 6, Issue 8 https://doi.org/10.1016/S0968-0896(98)00130-8	journal	August 1998
The development of proteasome inhibitors as anticancer drugs Adams, Julian Cancer Cell, Vol. 5, Issue 5 https://doi.org/10.1016/S1535-6108(04)00120-5	journal	May 2004
Mechanisms of transthyretin cardiomyocyte toxicity inhibition by resveratrol analogs Bourgault, Steve; Choi, Sungwook; Buxbaum, Joel N. Biochemical and Biophysical Research Communications, Vol. 410, Issue 4 https://doi.org/10.1016/j.bbrc.2011.04.133	journal	July 2011
Interactions between boric acid derivatives and saccharides in aqueous media: Structures and stabilities of resulting esters Peters, Joop A. Coordination Chemistry Reviews, Vol. 268 https://doi.org/10.1016/j.ccr.2014.01.016	journal	June 2014
Fast trigonal/tetragonal interconversion followed by slow chelate-ring closure in the complexation of boronic acids Yamamoto, Yoshiaki; Matsumura, Takeshi; Takao, Norihiro Inorganica Chimica Acta, Vol. 358, Issue 12 https://doi.org/10.1016/j.ica.2005.05.026	journal	August 2005
The Transthyretin Amyloidoses: From Delineating the Molecular Mechanism of Aggregation Linked to Pathology to a Regulatory-Agency-Approved Drug Johnson, Steven M.; Connelly, Stephen; Fearns, Colleen Journal of Molecular Biology, Vol. 421, Issue 2-3 https://doi.org/10.1016/j.jmb.2011.12.060	journal	August 2012
Boronic Acid for the Traceless Delivery of Proteins into Cells Andersen, Kristen A.; Smith, Thomas P.; Lomax, Jo E. ACS Chemical Biology, Vol. 11, Issue 2 https://doi.org/10.1021/acschembio.5b00966	journal	December 2015
Native State Kinetic Stabilization as a Strategy To Ameliorate Protein Misfolding Diseases: A Focus on the Transthyretin Amyloidoses Johnson, Steven M.; Wiseman, R. Luke; Sekijima, Yoshiki Accounts of Chemical Research, Vol. 38, Issue 12 https://doi.org/10.1021/ar020073i	journal	December 2005
Boronate Oxidation as a Bioorthogonal Reaction Approach for Studying the Chemistry of Hydrogen Peroxide in Living Systems Lippert, Alexander R.; Van de Bittner, Genevieve C.; Chang, Christopher J. Accounts of Chemical Research, Vol. 44, Issue 9 https://doi.org/10.1021/ar200126t	journal	September 2011
Exploiting the Reversible Covalent Bonding of Boronic Acids: Recognition, Sensing, and Assembly Bull, Steven D.; Davidson, Matthew G.; van den Elsen, Jean M. H. Accounts of Chemical Research, Vol. 46, Issue 2 https://doi.org/10.1021/ar300130w	journal	November 2012
Transthyretin as both a Sensor and a Scavenger of β-Amyloid Oligomers Yang, Dennis T.; Joshi, Gururaj; Cho, Patricia Y. Biochemistry, Vol. 52, Issue 17 https://doi.org/10.1021/bi4001613	journal	April 2013
Recent Developments in the Chemistry and Biological Applications of Benzoxaboroles Adamczyk-Woźniak, Agnieszka; Borys, Krzysztof M.; Sporzyński, Andrzej Chemical Reviews, Vol. 115, Issue 11 https://doi.org/10.1021/cr500642d	journal	May 2015
A Stilbene That Binds Selectively to Transthyretin in Cells and Remains Dark until It Undergoes a Chemoselective Reaction To Create a Bright Blue Fluorescent Conjugate Choi, Sungwook; Ong, Derrick Sek Tong; Kelly, Jeffery W. Journal of the American Chemical Society, Vol. 132, Issue 45 https://doi.org/10.1021/ja104999v	journal	November 2010
Stilbene Vinyl Sulfonamides as Fluorogenic Sensors of and Traceless Covalent Kinetic Stabilizers of Transthyretin That Prevent Amyloidogenesis Suh, Eul Hyun; Liu, Yu; Connelly, Stephen Journal of the American Chemical Society, Vol. 135, Issue 47 https://doi.org/10.1021/ja408230k	journal	November 2013
Biochemical and Structural Evaluation of Highly Selective 2-Arylbenzoxazole-Based Transthyretin Amyloidogenesis Inhibitors Johnson, Steven M.; Connelly, Stephen; Wilson, Ian A. Journal of Medicinal Chemistry, Vol. 51, Issue 2 https://doi.org/10.1021/jm0708735	journal	January 2008
Modulation of the Fibrillogenesis Inhibition Properties of Two Transthyretin Ligands by Halogenation Cotrina, Ellen Y.; Pinto, Marta; Bosch, Lluís Journal of Medicinal Chemistry, Vol. 56, Issue 22 https://doi.org/10.1021/jm401061w	journal	November 2013
Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies ^† Johnson, Steven M.; Connelly, Stephen; Wilson, Ian A. Journal of Medicinal Chemistry, Vol. 51, Issue 20 https://doi.org/10.1021/jm800435s	journal	October 2008
Polyol Complexes and Structure of the Benzeneboronate Ion Lorand, John P.; Edwards, John O. The Journal of Organic Chemistry, Vol. 24, Issue 6 https://doi.org/10.1021/jo01088a011	journal	June 1959
Insights into the Strength and Origin of Halogen Bonding: The Halobenzene−Formaldehyde Dimer Riley, Kevin E.; Merz, Kenneth M. The Journal of Physical Chemistry A, Vol. 111, Issue 9 https://doi.org/10.1021/jp066745u	journal	March 2007
Mild and Rapid Hydroxylation of Aryl/Heteroaryl Boronic Acids and Boronate Esters with N -Oxides Zhu, Chen; Wang, Rui; Falck, J. R. Organic Letters, Vol. 14, Issue 13 https://doi.org/10.1021/ol301463c	journal	June 2012
Protein folding and misfolding Dobson, Christopher M. Nature, Vol. 426, Issue 6968 https://doi.org/10.1038/nature02261	journal	December 2003
Halogen bonds as orthogonal molecular interactions to hydrogen bonds Voth, Andrea Regier; Khuu, Patricia; Oishi, Keita Nature Chemistry, Vol. 1, Issue 1 https://doi.org/10.1038/nchem.112	journal	March 2009
Inhibition of Mcl-1 through covalent modification of a noncatalytic lysine side chain Akçay, Gizem; Belmonte, Matthew A.; Aquila, Brian Nature Chemical Biology, Vol. 12, Issue 11 https://doi.org/10.1038/nchembio.2174	journal	September 2016
Chemoselective small molecules that covalently modify one lysine in a non-enzyme protein in plasma Choi, Sungwook; Connelly, Stephen; Reixach, Natàlia Nature Chemical Biology, Vol. 6, Issue 2 https://doi.org/10.1038/nchembio.281	journal	December 2009
The amyloid state and its association with protein misfolding diseases Knowles, Tuomas P. J.; Vendruscolo, Michele; Dobson, Christopher M. Nature Reviews Molecular Cell Biology, Vol. 15, Issue 6 https://doi.org/10.1038/nrm3810	journal	May 2014
Phenylboronic acid-based glucose-responsive polymeric nanoparticles: synthesis and applications in drug delivery Ma, Rujiang; Shi, Linqi Polym. Chem., Vol. 5, Issue 5 https://doi.org/10.1039/C3PY01202F	journal	January 2014
LX.—Invertase: a contribution to the history of an enzyme or unorganised ferment O'Sullivan, C.; Tompson, Frederick W. J. Chem. Soc., Trans., Vol. 57, Issue 0 https://doi.org/10.1039/CT8905700834	journal	January 1890
Selective sensing of saccharides using simple boronic acids and their aggregates Wu, Xin; Li, Zhao; Chen, Xuan-Xuan Chemical Society Reviews, Vol. 42, Issue 20 https://doi.org/10.1039/c3cs60148j	journal	January 2013
Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade Bulawa, C. E.; Connelly, S.; DeVit, M. Proceedings of the National Academy of Sciences, Vol. 109, Issue 24 https://doi.org/10.1073/pnas.1121005109	journal	May 2012
Ligand binding at the transthyretin dimer–dimer interface: structure of the transthyretin–T4Ac complex at 2.2 Å resolution Neumann, Piotr; Cody, Vivian; Wojtczak, Andrzej Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 10 https://doi.org/10.1107/S0907444905022523	journal	September 2005
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Protein stability induced by ligand binding correlates with changes in protein flexibility Celej, María Soledad; Montich, Guillermo G.; Fidelio, Gerardo D. Protein Science, Vol. 12, Issue 7 https://doi.org/10.1110/ps.0240003	journal	July 2003
How Much Binding Affinity Can be Gained by Filling a Cavity? Kawasaki, Yuko; Chufan, Eduardo E.; Lafont, Virginie Chemical Biology & Drug Design, Vol. 75, Issue 2 https://doi.org/10.1111/j.1747-0285.2009.00921.x	journal	February 2010
Diflunisal for ATTR Cardiac Amyloidosis: diflunisal for ATTR cardiac amyloidosis Castaño, Adam; Helmke, Stephen; Alvarez, Julissa Congestive Heart Failure, Vol. 18, Issue 6 https://doi.org/10.1111/j.1751-7133.2012.00303.x	journal	July 2012
Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay Molina, Daniel Martinez; Jafari, Rozbeh; Ignatushchenko, Marina Science, Vol. 341, Issue 6141 https://doi.org/10.1126/science.1233606	journal	July 2013
Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect Eriksson, A.; Baase, W.; Zhang, X. Science, Vol. 255, Issue 5041, p. 178-183 https://doi.org/10.1126/science.1553543	journal	January 1992
Potent Kinetic Stabilizers That Prevent Transthyretin-Mediated Cardiomyocyte Proteotoxicity Alhamadsheh, M. M.; Connelly, S.; Cho, A. Science Translational Medicine, Vol. 3, Issue 97 https://doi.org/10.1126/scitranslmed.3002473	journal	August 2011
Protein Misfolding, Functional Amyloid, and Human Disease Chiti, Fabrizio; Dobson, Christopher M. Annual Review of Biochemistry, Vol. 75, Issue 1 https://doi.org/10.1146/annurev.biochem.75.101304.123901	journal	June 2006
An overview of drugs currently under investigation for the treatment of transthyretin-related hereditary amyloidosis Obici, Laura; Merlini, Giampaolo Expert Opinion on Investigational Drugs, Vol. 23, Issue 9 https://doi.org/10.1517/13543784.2014.922541	journal	May 2014
Neutralization of Transthyretin Reverses the Neuroprotective Effects of Secreted Amyloid Precursor Protein (APP) in APPSw Mice Resulting in Tau Phosphorylation and Loss of Hippocampal Neurons: Support for the Amyloid Hypothesis Stein, T. D. Journal of Neuroscience, Vol. 24, Issue 35 https://doi.org/10.1523/JNEUROSCI.2211-04.2004	journal	September 2004
Mechanisms of Transthyretin Inhibition of -Amyloid Aggregation In Vitro Li, X.; Zhang, X.; Ladiwala, A. R. A. Journal of Neuroscience, Vol. 33, Issue 50 https://doi.org/10.1523/JNEUROSCI.2561-13.2013	journal	December 2013
Complex of rat transthyretin with tetraiodothyroacetic acid refined at 2.1 and 1.8 A resolution. Muzioł, T.; Cody, V.; Luft, J. R. Acta Biochimica Polonica, Vol. 48, Issue 4 https://doi.org/10.18388/abp.2001_3853	journal	December 2001
Familial amyloidotic polyneuropathy: current and emerging treatment options for transthyretin-mediated amyloidosis Hund, Ernst The Application of Clinical Genetics https://doi.org/10.2147/TACG.S19903	journal	June 2012
Nanoscaled boron-containing delivery systems and therapeutic agents for cancer treatment Wang, Jing; Wu, Wei; Jiang, Xiqun Nanomedicine, Vol. 10, Issue 7 https://doi.org/10.2217/nnm.14.213	journal	April 2015
Strategies for discovering and derisking covalent, irreversible enzyme inhibitors Johnson, Douglas S.; Weerapana, Eranthie; Cravatt, Benjamin F. Future Medicinal Chemistry, Vol. 2, Issue 6 https://doi.org/10.4155/fmc.10.21	journal	June 2010

Cited By (3)

Rational Design, Synthesis, Characterization and Evaluation of Iodinated 4,4′-Bipyridines as New Transthyretin Fibrillogenesis Inhibitors Dessì, Alessandro; Peluso, Paola; Dallocchio, Roberto Molecules, Vol. 25, Issue 9 https://doi.org/10.3390/molecules25092213	journal	May 2020
Novel Carbazole‐Based N ‐Heterocyclic Carbene Ligands to Access Synthetically Relevant Stilbenes in Pd‐Catalyzed Coupling Processes Girase, Tejpalsingh Ramsingh; Kapdi, Anant R. Chemistry – An Asian Journal, Vol. 14, Issue 15 https://doi.org/10.1002/asia.201900419	journal	June 2019
Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins Hiller, Noemi de J.; Silva, Nayane A. A. e.; Faria, Robson X. ChemMedChem, Vol. 13, Issue 14 https://doi.org/10.1002/cmdc.201800206	journal	June 2018

Similar Records

Uncovering the mechanism of aggregation of human transthyretin

Journal Article · Sun Oct 11 20:00:00 EDT 2015 · Journal of Biological Chemistry · OSTI ID:1228108

Amyloid seeding of transthyretin by ex vivo cardiac fibrils and its inhibition

Journal Article · Wed Jun 27 20:00:00 EDT 2018 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1457595

A Substructure Combination Strategy To Create Potent and Selective Transthyretin Kinetic Stabilizers That Prevent Amyloidogenesis and Cytotoxicity

Journal Article · Fri Aug 13 00:00:00 EDT 2010 · J. Am. Chem. Soc. · OSTI ID:1002589

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Ligands
Monomers
Nanofibers
Organic compounds
Phytochemistry

Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation

Citation Formats

References (77)

Cited By (3)

Similar Records

Related Subjects