(A) 25 Adenosine 88 Adeno

Total Page:16

File Type:pdf, Size:1020Kb

(A) 25 Adenosine 88 Adeno 371 Index a aminoacyl-transfer RNA (tRNA) 88, A1B11 SIRT2-selective inhibitors 233, 90, 102 235 ARSs 90, 91 A2B57 SIRT2-selective inhibitors 233, aminoacyl-pdCpA dinucleotide with 235 91, 93 acridine 8 post-aminoacylation modification adenine (A) 25 93 adenosine 88 preparing noncanonical 91 adenosine triphosphate (ATP) 8, 35, aminoacyl-tRNA synthetases (ARSs) 117 90–91, 96, 354 affinity-guided DMAP (AGD) 4-[(2-aminoethyl)carbomoyl]benzyl catalyst-mediated selective thioester (ABT) 95 chemical protein labeling 309 2-amino-4-pentenoic acid 98 affinity-guided DMAP AMPA receptors (4-dimethylaminopyridine) chemical labeling and fluorescent chemistry 309 visualization 303 affinity ligand-tethered DMAP catalyst FRAP analysis 304 309 anti-arrhythmic 43 [1-13C]alanine-NH2 282 antibody-drug conjugates (ADCs) 253 α-amino acid-based HP 13C chemical anti-cancer 43 probes 293 anticodon sequence 88 α-hydroxyl acids 95, 101 anti-malarial agents 43 amacrine/horizontal interneurons 78 antisense oligonucleotides (ASO) amino acids 258–260 incorporation of noncanonical aquaporin 183 101–103 4-armed star-shaped copolymers 209 misacylation of non-proteinogenic ASO conjugated with tocopherol 94–96 (Toc-ASO) 261–262 misincorporation 87 Aspidosperma alkaloids 45, 48, 49, 51, ribosomal translation 103, 104 64 aminoacylation assembly lines class I ARSs 90 artificial 68 ribozyme 94, 95 biogenetically inspired synthesis tRNA 90–91, 93, 95 58–68 aminoacyl dinucleotide 92 biomimetic 43, 52 Molecular Technology: Life Innovation, Volume 2, First Edition. Edited by Hisashi Yamamoto and Takashi Kato. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 372 Index assembly lines (contd.) budding 183 biosynthetic 45, 48, 58 bulk degradation 204 development of 45 bump and hole technology 313 Macmillan’s collective total synthesis 45–52 c nature of 62 [1-13C]α-amino acid 292, 293 synthesis of indole alkaloids 52–57 [1-13C]ascorbate 283–284 atomic force microscope (AFM) 29 13 C-benzylformic acid, for H2O2 detection 284 b [1-13C]bicarbonate,forpHsensing benzodiazepines 306 283 benzoxadiazole 124 [1-13C]dehydroascorbate 284 β-amino acids 87, 95, 335 [13C,D3]-p-anisidine 284–285 β-Cyclodextrin (β-CD) 190 cell-based yeast display method 347 bicycle-phage display approach 352 cell-cycle regulation 75 biodegradable poly(ether urethane) cell-free emulsion based encapsulation 213 method 347 biodegradable thermoplastics 207 cell-free ribosome display method 347 biogenetically inspired synthesis cell membranes 58–68 components of 118 biomimetic cyclization 49 negatively-charged 119 bioorthogonal reaction-based cell-penetrating peptides (CPP) 10 glycosylation 136 cell-surface AMPA receptors, diffusion 1,4-bis(4-phenylethynyl)benzene (BPEB) dynamics 302 units 186, 187 cellular uptake block catiomers efficiency 8, 10, 15 for gene delivery system 1–18 pDNA packaging 2–6 process 17 rod-shape/toroid-shape 17–18 rod-length limitation for 14 systemic gene therapy 14–16 CEST 126 13 blood cells 8 C-ethylenediaminetetraacetic acid blood circulation (EDTA) 285–286 13 of biological compounds 8 C-ethyleneglycol tetraacetic acid 286 capability 14 C–H activation reaction 224–228 capacity 2, 9, 14 chondroitin sulfate (HS) 8 13 in longevity 8 C hyperpolarized molecular probes molecular weight on 115 aminopeptidase N detection time 115 282–283 blood flow 73 [1-13C]ascorbate 283–284 blood vessel 13C-benzylformic acid 284 endothelial cells 114 [1-13C]bicarbonate 283 formation 73 [1-13C]dehydroascorbate 284 BNA/LNA chemistry 260 [13C,D]EDTA 285–286 13 Borromean rings 28 [ C,D3]-p-anisidine 284–285 bow-tie-shape dendrimers 115, 116 [1-13C]pyruvate 277–278 brain-derived neurotrophic factor chemical environment analysis 283 (BDNF) 80 enzymatic activity analysis 277 Index 373 γ-glutamyl transpeptidase 278–281 dissolution dynamic nuclear glycolysis and tricarboxylic acid cycle polarization process 274 analysis 278 1,2-distearoyl-sn-glycero- scaffold structure 292 3-phosphocholine (DSPC) 191 circular dichroism (CD) spectra 188 disuccinimidyl glutarate crosslinker click chemistry approach 352 HDAC3-selective inhibitor disulfide bond 10 identification 221–224 DMAP-antibody conjugates 312 HDAC8-selective inhibitor DMAP-tethered lectins 310 identification 224 DMF 6 SIRT2-selective inhibitors 232–234 DNA-based molecular technologies coordination chemistry-based fluorescence blinking control chemogenetic approach 171–177 312–320 genetic alphabet expansion copper-catalyzed cycloaddition 136 168–171 Coulomb repulsion 118, 120, 122 DNA computing 36 cyanomethyl ester (CME) 94 DNA condensation 1, 5, 18 cyclic peptides 329 DNA duplex 35 cyclization, of peptides 349 DNA forceps 33 cyclosporin 336, 337 DNA intercalators 8 cysteine conjugation 133–136 DNA nanorobot 33 cytidine 88 DNA nanotechnology 25, 26, 36 cytosine (C) 26 DNA origami box-shaped 3D 31 d design 31 d-α-amino acids 95 molecular machines made 33 d-amino acid 87, 101, 335 molecular peg board 32–33 degradation behavior of hydrogels 203 pinching devices 33–35 degree of polymerization (DP) 1, 4 2D nanostructures 31 degree of protonation 11 DNA packaging 1 deoxyribonucleic acids (DNA) 25, 339 DNA pliers 33, 35 characteristic of 26 DNA/RNA heteroduplex design principles 35 oligonucleotide (HDO) DNA-PAINT 36 concept 262–264 immobile DNA junctions 26–28 conjugated with tocopherol molecular architecture 25–36 (Toc-HDO) 264–268 molecule structure of 25–26 DNA sequence 105 nanostructures 25 DNA strands 26, 28 tiles and their assemblies 28–29 chemical synthesis of 339 topologically 28 DNA zipping mechanism 34 unzipping mechanism 35 double-stranded DNA 3 2′-deoxyribose ring 25 doxorubicin 120, 121 De-SPIO 118 DREADD technology 313 D-glucosamine 119 drug delivery system (DDS) 113 Diels–Alder cycloaddition 45 drug discovery platforms 104–105 diethylenetriamine (DET) 11 druggable proteins 330–332 374 Index Ds–Px pair 169 fluorescent imaging plate reader d-tyrosine 91 (FLIPRTM) 304 dynamic light scattering (DLS) 2 fluorescent labeling, of GABAA receptor 306 e fluorescent nanogel thermometer (FNT) eight-armed PEG 209 124 elastic pressure 204 fluorescent polymeric thermometer emitting fluorescent dye 36 (FPT) 124, 125 endosomal escape 15 fluorescent ZnII chemosensors 314 endosome escape 11–12 2-fluorodeoxy-d-glucose (2FDG) 117 endothelial cells formylmethionine (fMet) 89 growth 72 four-base codon method 98, 100 survival of 73 fucose-glycoconjugates 138 VEGFRs 73 functional peptides enhanced permeable retention (EPR) cell-based yeast display 347 effect 114, 117, 118, 123, 124, cell-free emulsion based 129 encapsulation methods 347 enzymatic activity, 13C molecular probes cell-free ribosome display 347 277 DNA sequencing techniques 346 enzymatic glycosylation 136–137 intracellular peptide selection 340–341 epidermal growth factor receptor mRNA-display method 345–347 (EGFR) 9 natural peptide synthesis 339–340 epigenetics 219–221 phage display method 341–345 ethylene diamine (EDA) 11 ribosomal synthesis 337–339 extracellular matrix (ECM) 74, 78, 118, 119 g GABAA receptors 306, 307 f galactose-modified proteins 137 flavin adenine dinucleotide (FAD) 239 gamma-aminobutyric acid (GABA) flexizymes 355–356 306 Flory–Rehner model 204 γ-amino acids 95 fluorescence 139, 147, 152 γ-glutamyl-[1-13C]glycine fluorescence-activated cell sorting (γ-Glu-[1-13C]Gly) 278–279, (FACS) device 33 281 fluorescence blinking γ-glutamyl transpeptidase (GGT) blinking kinetics 172 analysis 278–281 isomerization blinking 176 GB-GC-SPIO 118 redox blinking 175 GC-SPIO 117, 119 single molecule detection 171 gene delivery triplet blinking 174 impact for 6 fluorescence correlation spectroscopy nuclease attack 6 (FCS) 172 polyplex micelles 6–14 fluorescence recovery after gene silencing photobleaching (FRAP) method after ASO or Toc-HDO injection 302 265 fluorescent biosensors 305 Toc-ASO 262 Index 375 gene therapy 14–16 h genetic alphabet expansion HDAC3-selective inhibitors 221–224 high-affinity DNA aptamer HDAC6-insensitive inhibitors generation 169 224–228 nucleotide modifications 168 HDAC8-selective inhibitors 224 unnatural base-pair 168 HDO Conjugated with Tocopherol genetic code (Toc-HDO) decoding 88–90 adverse effect 266–268 expansion 352 on ApoB mRNA levels 265 flexizymes 355–356 construction 264 in vitro chemical ligation approach design 264 353 mechanism 268 limitation 354 potency 264–266 messenger RNA (mRNA) Heck cyclization 49 88, 90 Henderson–Hasselbalch equation non-standard base method 101 283 RaPID system 356–361 heparan sulfate (HS) 8 reprogramming 97–98 hexaethylene glycol chains 127 glomerular cells 115, 116 hexammine cobalt 17 glycan molecule technology 132 histone bioorthogonal reaction-based acetylation and methylation 219, glycosylation 136 220 cysteine conjugation 133–136 chemical modification 220 enzymatic glycosylation histone deacetylase (HDAC) inhibitors 136–137 221 in vivo organ selective Au-catalyzed HDAC3-selective inhibitors reactivity 153 221–224 on live cells 148–150 HDAC6-insensitive inhibitors lysine conjugation 133 224–228 as metal carriers 151 HDAC6-selective inhibitors 228, glycans 132 229 natural 155 HDAC8-selective inhibitors 224, protein-conjugation 133 225 glycol chitosan (GC) 117 SIRT1-selective inhibitors 228–232 glycolide 207 SIRT2-selective inhibitors 232–234 glycolysis 117 histone lysine demethylase (KDM) glycoprotein labeling, with inhibitors DMAP-tethered lectin 311 KDM4C inhibitors 235–237 glycosaminoglycans (GAGs) 8–10 KDM5A inhibitor identification gold nanoparticles 32 237–238 gold nanorods 32 KDM7B inhibitor identification G-quadruplex formation 35 238–239
Recommended publications
  • Chemical Genomics 33
    Curr. Issues Mol. Biol. (2002) 4: 33-43. Chemical Genomics 33 Chemical Genomics: A Systematic Approach in Biological Research and Drug Discovery X.F. Steven Zheng1* and Ting-Fung Chan2 synthesis (Russell and Eggleston 2000) and new screening technologies such as small chemical compound (MacBeath 1Department of Pathology and Immunology and 2Molecular et al. 1999) and protein microarrays (MacBeath and and Cellular Biology Program, Campus Box 8069 Schreiber 2000; Zhu et al. 2000; Haab et al. 2001). In this Washington University School of Medicine article, we will provide a detailed analysis of the current 660 South Euclid Avenue, St. Louis, Missouri 63110 USA state of chemical genomics and its potential impact on biological and medical research, and pharmaceutical development. Abstract Chemical Biology or Genetics The knowledge of complete sequences of different organisms is dramatically changing the landscape of Since the seminal study of pea genetics by Mendal in 1865, biological research and pharmaceutical development. genetic analysis has been the benchmark for understanding We are experiencing a transition from a trial-and-error gene or protein functions. In classical genetics or forward approach in traditional biological research and natural genetics, the genomic DNA of a model organism or cell is product drug discovery to a systematic operation in randomly mutagenized to generate large numbers of genomics and target-specific drug design and mutants, which are screened for a desirable phenotype or selection. Small, cell-permeable and target-specific trait, such as alteration in growth, appearance or behavior. chemical ligands are particularly useful in systematic The phenotypes are then used to identify the responsible genomic approaches to study biological questions.
    [Show full text]
  • What Are We Missing by Using Hydrophilic Enrichment? Improving Bacterial Glycoproteome
    bioRxiv preprint doi: https://doi.org/10.1101/2020.07.22.216903; this version posted July 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. 1 What are we missing by using hydrophilic enrichment? Improving bacterial glycoproteome 2 coverage using total proteome and FAIMS analysis. 3 4 Ameera Raudah Ahmad Izaham1 Ching-Seng Ang2, Shuai Nie2, Lauren E. Bird1, Nicholas A. 5 Williamson2 and Nichollas E. Scott1# 6 7 1Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty 8 Institute for Infection and Immunity, Melbourne 3000, Australia 9 2Melbourne Mass Spectrometry and Proteomics Facility, The Bio21 Molecular Science and 10 Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia. 11 12 13 14 Running title: identifying HILIC inaccessible glycopeptides within bacterial glycoproteomes 15 16 17 18 19 20 Keywords: Glycoproteomics, FAIMS, HILIC, Glycopeptide enrichment, Bacterial glycosylation, 21 Burkholderia 22 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.22.216903; this version posted July 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. 23 ABSTRACT 24 Hydrophilic Interaction Liquid Chromatography (HILIC) glycopeptide enrichment is an 25 indispensable tool for the high-throughput characterisation of glycoproteomes. Despite its utility, 26 HILIC enrichment is associated with a number of short comings including requiring large amounts 27 of starting material, potentially introducing chemical artefacts such as formylation, and 28 biasing/under-sampling specific classes of glycopeptides.
    [Show full text]
  • University of Dundee New Synthetic Routes to Triazolo
    University of Dundee New synthetic routes to Triazolo-benzodiazepine analogues Baud, Matthias G. J.; Lin-Shiao, Enrique; Zengerle, Michael; Tallant, Cynthia; Ciulli, Alessio Published in: Journal of Medicinal Chemistry DOI: 10.1021/acs.jmedchem.5b01135 Publication date: 2016 Document Version Publisher's PDF, also known as Version of record Link to publication in Discovery Research Portal Citation for published version (APA): Baud, M. G. J., Lin-Shiao, E., Zengerle, M., Tallant, C., & Ciulli, A. (2016). New synthetic routes to Triazolo- benzodiazepine analogues: expanding the scope of the bump-and-hole approach for selective Bromo and Extra- Terminal (BET) bromodomain inhibition. Journal of Medicinal Chemistry, 59(4), 1492-1500. DOI: 10.1021/acs.jmedchem.5b01135 General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal. Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 17. Feb. 2017 This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
    [Show full text]
  • University of Dundee Chemical Genetics Approaches For
    CORE Metadata, citation and similar papers at core.ac.uk Provided by University of Dundee Online Publications University of Dundee Chemical genetics approaches for selective intervention in epigenetics Runcie, Andrew C.; Chan, Kwok Ho; Zengerle, Michael; Ciulli, Alessio Published in: Current Opinion in Chemical Biology DOI: 10.1016/j.cbpa.2016.06.031 Publication date: 2016 Document Version Publisher's PDF, also known as Version of record Link to publication in Discovery Research Portal Citation for published version (APA): Runcie, A. C., Chan, K. H., Zengerle, M., & Ciulli, A. (2016). Chemical genetics approaches for selective intervention in epigenetics. Current Opinion in Chemical Biology, 33, 186-194. DOI: 10.1016/j.cbpa.2016.06.031 General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal. Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 17. Feb. 2017 Available online at www.sciencedirect.com ScienceDirect Chemical genetics approaches for selective intervention in epigenetics Andrew C Runcie, Kwok-Ho Chan, Michael Zengerle and Alessio Ciulli Chemical genetics is the use of biologically active small [3], but alters a different point in the gene–protein–pheno- molecules (chemical probes) to investigate the functions of type relationship.
    [Show full text]
  • Chemical Genetics Approaches for Selective Intervention in Epigenetics Runcie, Andrew C.; Chan, Kwok Ho; Zengerle, Michael; Ciulli, Alessio
    University of Dundee Chemical genetics approaches for selective intervention in epigenetics Runcie, Andrew C.; Chan, Kwok Ho; Zengerle, Michael; Ciulli, Alessio Published in: Current Opinion in Chemical Biology DOI: 10.1016/j.cbpa.2016.06.031 Publication date: 2016 Licence: CC BY-NC-ND Document Version Publisher's PDF, also known as Version of record Link to publication in Discovery Research Portal Citation for published version (APA): Runcie, A. C., Chan, K. H., Zengerle, M., & Ciulli, A. (2016). Chemical genetics approaches for selective intervention in epigenetics. Current Opinion in Chemical Biology, 33, 186-194. https://doi.org/10.1016/j.cbpa.2016.06.031 General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal. Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 30. Sep. 2021 Available online at www.sciencedirect.com ScienceDirect Chemical genetics approaches for selective intervention in epigenetics Andrew C Runcie, Kwok-Ho Chan, Michael Zengerle and Alessio Ciulli Chemical genetics is the use of biologically active small [3], but alters a different point in the gene–protein–pheno- molecules (chemical probes) to investigate the functions of type relationship.
    [Show full text]
  • Synthesis and Investigation of Bacterial Effector Molecules
    Synthesis and investigation of bacterial effector molecules Michael Franz Albers Doctoral Thesis, Department of Chemistry Umeå University, 2016 Responsible publisher under swedish law: the Dean of the Faculty of Science and Technology This work is protected by the Swedish Copyright Legislation (Act 1960:729) ISBN: 978-91-7601-411-0 Electronic version available at http://umu.diva-portal.org/ Tryck/Printed by: VMC-KBC Umeå Umeå, Sweden, 2016 Table of Contents Table of Contents i Abstract iii List of Abbreviations iv List of Publications vii Author contributions viii Papers by the author, but not included in this thesis viii Enkel sammanfattning på svenska ix Introduction 1 Post-translational modifications 1 Nucleotidylylation and phosphocholination 2 Small GTPases 7 Pathogens modify host cells at a molecular level 9 Quorum sensing in Legionella pneumophila 12 Proteomics towards PTMs 13 Chapter 1: Towards the identification of adenylylated proteins and adenylylation-modifying enzymes (Paper I – III) 19 Previous work 19 Outline: From building blocks to antibodies 22 Synthesis of a tyrosine-AMP building block 23 Synthesis of a threonine- and serine-AMP building block 26 Synthesis of adenylylated Peptides 28 Generation of AMP specific antibodies 30 Mass fragmentation patterns of adenylylated peptides 37 Immunoprecipitation of adenylylated proteins 42 Non-hydrolysable mimics for the study of deadenylylating enzymes 47 Future work 52 Ongoing Work – Covalent trapping of substrates of adenylyl transferases 53 Conclusions 60 Chapter 2: Tools for
    [Show full text]
  • Development of ATP-Based Signaling Molecules
    Development of ATP-based Signaling Molecules Dissertation zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr.rer.nat.) vorgelegt von Susanne Ermert aus Bad Neuenahr-Ahrweiler an der Mathematisch-Naturwissenschaftliche Sektion Fachbereich Chemie Konstanz, 2018 Konstanzer Online-Publikations-System (KOPS) URL: http://nbn-resolving.de/urn:nbn:de:bsz:352-2-fd0z6lhm2fea9 Tag der mündlichen Prüfung: 24. Juli 2018 1. Referent: Prof. Dr. Andreas Marx 2. Referent: Prof. Dr. Martin Scheffner “Was man zu verstehen gelernt hat, fürchtet man nicht mehr.“ Marie Curie I II This work was prepared from April 2015 to June 2018 in the group of Prof. Dr. Andreas Marx (Chair of Organic and Cellular Chemistry) at the University of Konstanz. It was funded by the SFB 969 (Chemical and Biological Principles of Cellular Proteostasis) and supported by the Konstanz Research School Chemical Biology. Parts of this work have been published and were reproduced with permission: S. Ermert, S. M. Hacker, A. Buntru, M. Scheffner, C. R. Hauck and A. Marx, ChemBioChem 2017, 18, 378-381. Copyright 2017 Wiley-VCH. S. Ermert, A. Marx and S. M. Hacker, Top Curr Chem 2017, 375: 28. Copyright 2017 Springer International Publishing Switzerland. III IV Publications and Communications Parts of this work have been published. Journal Publications: S. Ermert, S. M. Hacker, A. Buntru, M. Scheffner, C. R. Hauck and A. Marx, ChemBioChem 2017, 18, 378-381. “Different Enzymatic Processing of -Phosphoramidate and -Phosphoester-Modified ATP Analogues” S. Ermert, A. Marx and S. M. Hacker, Top Curr Chem 2017, 375: 28. “Phosphate-Modified Nucleotides for Monitoring Enzyme Activity” in “Phosphate Labeling in Chemical Biology” edited by Henning Jessen Poster Presentations: S.
    [Show full text]
  • 7Th Annual Kinase Inhibitor Chemistry
    Cover ELEVENTH ANNUAL Conference-at-a-Glance Welcome Letter Short Courses Drug Discovery Distinguished Faculty Inflammation Inhibitors Protein-Protein Interactions ChemistryAPRIL 19 - 22, 2016 HILTON SAN DIEGO RESORT & SPA | SAN DIEGO, CA Epigenetic Inhibitor Discovery Kinase Inhibitor Chemistry OPTIMIZING SMALL MOLECULES April 19 - 20 Macrocylics & Constrained FOR TOMORROW’S THERAPEUTICS Peptides Inflammation Inhibitors Fragment-Based Drug Discovery PLENARY KEYNOTES Protein-Protein Interactions Brain Penetrant Inhibitors A Chemist’s Foray into Translational Research Biophysical Approaches for Epigenetic Inhibitor Discovery Drug Discovery Peter G. Schultz, Ph.D., The Scripps Research Institute Antivirals: Small Molecule April 20 - 21 Inhibitors of Viral Targets Cell-Penetrating Miniproteins Applying Pharmacology to Gregory L. Verdine, Ph.D., New Drug Discovery Harvard University Kinase Inhibitor Chemistry Sponsor & Exhibit Opportunities Macrocyclics & Constrained Peptides Hotel & Travel Information EVENT FEATURES • More than 125 presentations Fragment-Based Drug Discovery Registration Information • 600+ high-level participants • 70+ posters Click Here to • Interactive roundtable, breakout SYMPOSIA Friday, April 22 Register Online! & panel discussions DrugDiscoveryChemistry.com • “Track-hop” between concurrent meetings Brain Penetrant Inhibitors • Exclusive exhibit & poster viewing hours • Dedicated networking opportunities Biophysical Approaches for Drug Discovery FINAL DAYS • 10 interactive short courses TO REGISTER! Antivirals: Small
    [Show full text]
  • Chemical Precision Glyco-Mutagenesis by Glycosyltransferase Engineering in Living Cells
    bioRxiv preprint doi: https://doi.org/10.1101/669861; this version posted June 13, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Chemical precision glyco-mutagenesis by glycosyltransferase engineering in living cells Benjamin Schumann1£, Stacy A. Malaker1$, Simon P. Wisnovsky1$, Marjoke F. Debets1±, Anthony 5 J. Agbay1, Daniel Fernandez3, Lauren J. S. Wagner4, Liang Lin5, Junwon Choi1#, Douglas M. Fox1, Jessie Peh1, Melissa A. Gray1, Kayvon Pedram1, Jennifer J. Kohler6, Milan Mrksich5, Carolyn R. Bertozzi1,2* 1Department of Chemistry, Stanford University, 380 Roth Way, Stanford, CA94305, USA. 2Howard Hughes Medical Institute, 380 Roth Way, Stanford, CA94305, USA. 10 3Stanford ChEM-H Macromolecular Structure Knowledge Center, 443 Via Ortega, Stanford, CA. 4Department of Chemistry, University of California, Berkeley, CA 94720, USA. 5Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Rd, Tech B492, Evanston, IL-60208, USA. 6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 15 75390-9038, USA. £Current address: The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK, and Imperial College London, 80 Wood Lane, London W12 0BZ, UK. ±Current address: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA 20 #Current address: Korea Institute of Science and Technology, Hwarangro 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea. $These authors contributed equally. *Corresponding author: [email protected] 25 1 bioRxiv preprint doi: https://doi.org/10.1101/669861; this version posted June 13, 2019.
    [Show full text]
  • Chemical Manipuration of Protein Functions
    Chemical Manipulation of Protein Functions -Utilizing incorporation of a genetically encoded unnatural amino acid- Literature Seminar 20th Oct 2016 Kai Kitamura Outline 1. Introduction 2. Incorporation of unnatural amino acids 3. Bioorthogonal ligand tethering (BOLT) 4. Protein-control using Staudinger reduction (Main Paper) 5. Summary 2 Introduction Why is “protein-manipulation” required? Biochemistry: traditionally focused on the study in vitro (in a reconstituted system) it cannot fully mimic a biological system Factors such as: • Dosage • Intracellular Localization • Timing • Intermolecular Interactions are important in living systems Hahn, M.E.; Muir, T. W. TRENDS in Biochem. Sci. 2005, 30, 1 3 Introduction What is the ideal “protein-manipulation” method? - immediate on/off switching of protein functions - high selectivity of inhibition/activation (even between very similar isozymes) - in cell (in vivo) applicability - usability of the method - versatile applicability to various proteins Rationally designed chemistry-driven strategies have appeared 4 How to Control Proteins with Chemistry 1. (Inhibitors) 2. Expressed Protein Ligation (EPL) 3. Conditional Protein Splicing 4. Conditional Protein Degradation 5. Bump-and-Hole Strategy 6. Site-directed Unnatural Amino Acid Mutagenesis Protein engineering techniques are indispensable 5 Intein-based Semi-synthesis (EPL: Expressed Protein Ligation) Intein: Intron in protein processing/ CBD: Chitin-binding domain Seyedsayamdost, M. R.; Yee, C. S. and Stubbe, J. Nat. Protocol 2007, 2, 1225 6 Lu, W et al. Mol. Cell 2001, 8, 759 Conditional Protein Splicing Intein: Intron in protein processing/ FKBP: FK506-binding protein 12/ ERB: FKBP-rapamycin binding protein divided protein of interest protein of interest (inactive form) (active form) Mootz, H. D.; Blum, E.
    [Show full text]
  • Chemical Genetics Approaches for Selective Intervention in Epigenetics
    Available online at www.sciencedirect.com ScienceDirect Chemical genetics approaches for selective intervention in epigenetics Andrew C Runcie, Kwok-Ho Chan, Michael Zengerle and Alessio Ciulli Chemical genetics is the use of biologically active small [3], but alters a different point in the gene–protein–pheno- molecules (chemical probes) to investigate the functions of type relationship. Classical genetics typically intervenes gene products, through the modulation of protein activity. upon the gene itself (or RNA), altering or down-regulating Recent years have seen significant progress in the application the protein as a result; whereas chemical genetics affects the of chemical genetics to study epigenetics, following the behavior of the protein directly. development of new chemical probes, a growing appreciation of the role of epigenetics in disease and a recognition of the Chemical genetics has several advantages over classical need and utility of high-quality, cell-active chemical probes. In genetics [3]; such as reversibility, tuneability and greater this review, we single out the bromodomain reader domains as spatial and temporal control. Genetic tools have addition- a prime example of both the success, and challenges facing al drawbacks, such as the potential lethality of knock- chemical genetics. The difficulty in generating single-target outs. However, chemical probes are typically less selec- selectivity has long been a thorn in the side of chemical tive than targeted gene-modification and may be active genetics, however, recent developments in advanced forms of against several related proteins, preventing the connec- chemical genetics promise to bypass this, and other, tion of specific functions and phenotypes with specific limitations.
    [Show full text]
  • Chemical Biology Strategies for Posttranslational Control of Protein Function
    Chemistry & Biology Review Chemical Biology Strategies for Posttranslational Control of Protein Function Rishi Rakhit,1 Raul Navarro,1 and Thomas J. Wandless1,* 1Department of Chemical & Systems Biology, Stanford University, Stanford, CA 94305, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.chembiol.2014.08.011 A common strategy to understand a biological system is to selectively perturb it and observe its response. Although technologies now exist to manipulate cellular systems at the genetic and transcript level, the direct manipulation of functions at the protein level can offer significant advantages in precision, speed, and revers- ibility. Combining the specificity of genetic manipulation and the spatiotemporal resolution of light- and small molecule-based approaches now allows exquisite control over biological systems to subtly perturb a system of interest in vitro and in vivo. Conditional perturbation mechanisms may be broadly characterized by change in intracellular localization, intramolecular activation, or degradation of a protein-of-interest. Here we review recent advances in technologies for conditional regulation of protein function and suggest further areas of potential development. Mechanistic understanding of cell biology and physiology is on the functional molecule. Directly targeting proteins via small- driven in part by the tools available to manipulate the system molecule inhibitors or activators is fast, conditional, and simple and to assay the phenotypic response. The study of a particular if a perturbant is available but may be limited by specificity and process requires specialized approaches to enable dissection of exhibit off-target effects (Fabian et al., 2005; Lounkine et al., components, connectivity, and, ultimately, causation. A wide 2012).
    [Show full text]