Helena Danielson
Professor at Institutionen för kemi - BMC; Biokemi; Danielson grupp
- Telephone:
- +46 18 471 45 45
- Mobile phone:
- +46 70 425 01 03
- E-mail:
- Helena.Danielson@kemi.uu.se
- Visiting address:
- Husargatan 3
752 37 Uppsala - Postal address:
- Box 576
75123 Uppsala
- ORCID:
- 0000-0003-2728-0340
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Short presentation
Enzymology and drug discovery
Biography
Professor of Biochemistry at Uppsala University in Sweden since 2002. Platform Scientific Director at the SciLifeLab infrastructure unit for Biophysical Screening and Characterization and co-founder of Beactica Therapeutics AB.
Specialist in enzymology and drug discovery with a focus on biomolecular interaction analysis for detailed studies of enzyme-inhibitor interactions and other important recognition processes in the life science area. The work has involved studies of a variety of enzymes, primarily proteases and polymerases from viruses and other infectious organisms, or involved in important disease processes. Extensive experience of the commercial drug discovery process through over 30 years of collaborative research with partners in pharmaceutical and biotechnological industry.
Publications
Selection of publications
- Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ (2022)
- Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses (2022)
- Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor (2021)
- Discovery of an allosteric ligand binding site in SMYD3 lysine methyltransferase (2021)
- Unveiling the Biochemistry of the Epigenetic Regulator SMYD3 (2019)
- Introduction of Intrinsic Kinetics of Protein-Ligand Interactions and Their Implications for Drug Design (2018)
- Biophysics in drug discovery (2016)
Recent publications
- Multiplexed experimental strategies for fragment library screening against challenging drug targets using SPR biosensors (2024)
- The Allosteric Regulation of Β-Ureidopropionase Depends on Fine-Tuned Stability of Active-Site Loops and Subunit Interfaces (2023)
- The Crystal Structure of Tyrosinase from Verrucomicrobium spinosum Reveals It to Be an Atypical Bacterial Tyrosinase (2023)
- Amino acid substitutions in human growth hormone affect secondary structure and receptor binding (2023)
- Amino acid substitutions in human growth hormone affect secondary structure and receptor binding (2023)
All publications
Articles
- Multiplexed experimental strategies for fragment library screening against challenging drug targets using SPR biosensors (2024)
- The Allosteric Regulation of Β-Ureidopropionase Depends on Fine-Tuned Stability of Active-Site Loops and Subunit Interfaces (2023)
- The Crystal Structure of Tyrosinase from Verrucomicrobium spinosum Reveals It to Be an Atypical Bacterial Tyrosinase (2023)
- Amino acid substitutions in human growth hormone affect secondary structure and receptor binding (2023)
- Amino acid substitutions in human growth hormone affect secondary structure and receptor binding (2023)
- Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ (2022)
- Sensitive protein detection using site-specifically oligonucleotide-conjugated nanobody reagents (2022)
- Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses (2022)
- Discovery of the 4-aminopiperidine-based compound EM127 for the site-specific covalent inhibition of SMYD3 (2022)
- Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor (2021)
- Discovery of an allosteric ligand binding site in SMYD3 lysine methyltransferase (2021)
- A real-time cell-binding assay reveals dynamic features of STxB-Gb3 cointernalization and STxB-mediated cargo delivery into cancer cells (2020)
- Establishing Trypanosoma cruzi farnesyl pyrophosphatesynthase as a viable target for biosensor driven fragment-based lead discovery (2020)
- Estimating Detection Limits of Potentiometric DNA sensors Using Surface Plasmon Resonance Analyses (2020)
- Macrocyclic Peptides Uncover a Novel Binding Mode for Reversible Inhibitors of LSD1 (2020)
- Fibrin fragment E potentiates TGF-beta-induced myofibroblast activation and recruitment (2020)
- Unveiling the Biochemistry of the Epigenetic Regulator SMYD3 (2019)
- Structural Changes of Mercaptohexanol Self-assembled Monolayers on Gold and their Influence on Impedimetric Aptamer Sensors (2019)
- Pan-NS3 protease inhibitors of hepatitis C virus based on an R3-elongated pyrazinone scaffold (2018)
- Introduction of Intrinsic Kinetics of Protein-Ligand Interactions and Their Implications for Drug Design (2018)
- Noelin1 Affects Lateral Mobility of Synaptic AMPA Receptors (2018)
- Biophysical Mode-of-Action and Selectivity Analysis of Allosteric Inhibitors of Hepatitis C Virus (HCV) Polymerase (2017)
- Monitoring drug-serum protein interactions for early ADME prediction through Surface Plasmon Resonance technology (2017)
- Intrinsic vs. observed thermodynamic and kinetic parameters of carbonic anhydrase-ligand interaction (2017)
- Intrinsic vs. observed thermodynamic and kinetic parameters of carbonic anhydrase-ligand interaction (2017)
- Insights from engineering the Affibody-Fc interaction with a computational-experimental method (2017)
- Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously (2017)
- Biophysical analysis of the dynamics of calmodulin interactions with neurogranin and Ca2+/calmodulin-dependent kinase II (2017)
- Characterization of interactions between hepatitis C virus NS5B polymerase, annexin A2 and RNA - effects on NS5B catalysis and allosteric inhibition (2017)
- Discovery of pyrazinone based compounds that potently inhibit the drug resistant enzyme variant R155K of the hepatitis C virus NS3 protease (2016)
- Let There Be Light! (2016)
- Biophysics in drug discovery (2016)
- Kinetically Selective Inhibitors of Human Carbonic Anhydrase Isozymes I, II, VII, IX, XII, and XIII (2016)
- Identification and Characterization of an Irreversible Inhibitor of CDK2 (2015)
- Analysis of the leakage of gene repression by an artificial TetR-regulated promoter in cyanobacteria (2015)
- Analysis of the leakage of gene repression by an artificial TetR-regulated promoter in cyanobacteria (2015)
- Proximity-dependent initiation of hybridization chain reaction (2015)
- Molecular blueprint of allosteric binding sites in a homologue of the agonist-binding domain of the alpha 7 nicotinic acetylcholine receptor (2015)
- Accounting for strain variations and resistance mutations in the characterization of hepatitis C NS3 protease inhibitors (2014)
- Achiral Pyrazinone-Based Inhibitors of the Hepatitis C Virus NS3 Protease and Drug-Resistant Variants with Elongated Substituents Directed Toward the S2 Pocket (2014)
- Vinylated linear P2 pyrimidinyloxyphenylglycine based inhibitors of the HCV NS3/4A protease and corresponding macrocycles (2014)
- Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2–P1′ Region (2014)
- The Versatile Nature of the 6-Aminoquinolone Scaffold (2014)
- Identification and characterization of an irreversible inhibitor of CDK2 (2014)
- Identification of weak points of hepatitis C virus NS3 protease inhibitors using surface plasmon resonance biosensor-based interaction kinetic analysis and genetic variants (2014)
- Identification of Weak Points of Hepatitis C Virus NS3 Protease Inhibitors Using Surface Plasmon Resonance Biosensor-Based Interaction Kinetic Analysis and Genetic Variants (2014)
- Structure-Based Discovery of Pyrazolobenzothiazine Derivatives As Inhibitors of Hepatitis C Virus Replication (2013)
- Efficient Screening of Marine Extracts for Protease Inhibitors by Combining FRET Based Activity Assays and Surface Plasmon Resonance Spectroscopy Based Binding Assays (2013)
- The advantage of biosensor analysis over enzyme inhibition studies for slow dissociating inhibitors (2013)
- Structural basis of ligand recognition in 5-HT3 receptors (2013)
- On the Active Site Protonation State in Aspartic Proteases (2013)
- Resolution of the Interaction Mechanisms and Characteristics of Non-nucleoside Inhibitors of Hepatitis C Virus Polymerase - Laying the Foundation for Discovery of Allosteric HCV Drugs (2013)
- Identification of Structural-Kinetic and Structural-Thermodynamic Relationships for Thrombin Inhibitors (2013)
- Experimental and 'in silico' analysis of the effect of pH on HIV-1 protease inhibitor affinity (2012)
- AKAP79/150 interacts with the neuronal calcium-binding protein caldendrin (2012)
- Aliskiren displays long-lasting interactions with human renin (2012)
- Histaminergic pharmacology of homo-oligomeric beta 3 gamma-aminobutyric acid type A receptors characterized by surface plasmon resonance biosensor technology (2012)
- Kinetic and mechanistic differences in the interactions between caldendrin and calmodulin with AKAP79 suggest different roles in synaptic function (2012)
- Synthesis and SAR Around the R6 Position of 2(1H)-Pyrazinone Based HCV NS3 Protease Inhibitors (2011)
- Deconstruction of Non-Nucleoside Reverse Transcriptase Inhibitors of Human Immunodeficiency Virus Type 1 for Exploration of the Optimization Landscape of Fragments (2011)
- A surface plasmon resonance-based biosensor with full-length BACE1 in a reconstituted membrane (2011)
- Experimental Validation of a Fragment Library for Lead Discovery Using SPR Biosensor Technology (2011)
- Mechanistic and kinetic characterization of hepatitis C virus NS3 protein interactions with NS4A and protease inhibitors (2011)
- Identification of a Novel Scaffold for Allosteric Inhibition of Wild Type and Drug Resistant HIV-1 Reverse Transcriptase by Fragment Library Screening (2011)
- Quantification of interactions between drug leads and serum proteins by use of "binding efficiency" (2011)
- P2-P1 ' macrocyclization of P2 phenylglycine based HCV NS3 protease inhibitors using ring-closing metathesis (2011)
- Powerful protein binders from designed polypeptides and small organic molecules (2011)
- Hepatitis C Virus NS3 Protease Inhibitors based on 2(1H)-Pyrazinones (2010)
- Surface Plasmon Resonance Biosensor Based Fragment Screening Using Acetylcholine Binding Protein Identifies Ligand Efficiency Hot Spots (LE Hot Spots) by Deconstruction of Nicotinic Acetylcholine Receptor α7 Ligands (2010)
- Effect of the Protonation State of the Titratable Residues on the Inhibitor Affinity to BACE-1 (2010)
- Inhibition of HIV-1 by non-nucleoside reverse transcriptase inhibitors via an induced fit mechanism (2010)
- Interaction kinetic and structural dynamic analysis of ligand binding to acetylcholine-binding protein (2010)
- Hepatitis C protease inhibitors based on 2(1H)-pyrazinones (2010)
- Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents (2010)
- Biotinylated lipid bilayer disks as model membranes for biosensor analyses (2010)
- Development of surface plasmon resonance biosensor assays for primary and secondary screening of acetylcholine binding protein ligands (2010)
- Discovery of Achiral Inhibitors of the Hepatitis C Virus NS3 Protease based on 2(1H)-pyrazinones (2010)
- Structure-activity relationships of HCV NS3 protease inhibitors evaluated on the drug-resistant variants A156T and D168V (2010)
- HSA binding of HIV protease inhibitors (2009)
- Characterization of Ca2+ and phosphocholine interactions with C-reactive protein using a surface plasmon resonance biosensor (2009)
- Hepatitis C Virus NS3 Protease Is Activated by Low Concentrations of Protease Inhibitors (2009)
- Integrating surface plasmon resonance biosensor-based interaction kinetic analyses into the lead discovery and optimization process (2009)
- Fragment library screening and lead characterization using SPR biosensors (2009)
- Integrating surface plasmon resonance biosensor-based interaction kinetic analyses into the lead discovery and optimization process (2009)
- Screening for NNRTIs with Slow Dissociation and High Affinity for a Panel of HIV-1 RT Variants (2009)
- Structural and Functional Analysis of Hepatitis C Virus Strain JFH1 Polymerase (2009)
- A protein interaction node at the neurotransmitter release site (2009)
- MIV-170, a novel NNRTI exhibiting tight binding to HIV-1 reverse transcriptase (RT) (2008)
- Identification of MMP-12 Inhibitors by Using Biosensor-Based Screening of a Fragment Library (2008)
- β-Amino acid substitutions and structure-based CoMFA modeling of hepatitis C virus NS3 protease inhibitors (2008)
- Hepatitis C Virus NS3 Protease Inhibitors Comprising a Novel Aromatic P1 Moiety (2008)
- Resistance profiling of hepatitis C virus protease inhibitors using full-length NS3 (2007)
- Effects on protease inhibition by modifying of helicase residues in hepatitis C virus nonstructural protein 3 (2007)
- Additional level of information about complex interaction between non-nucleoside inhibitor and HIV-1 reverse transcriptase using biosensor-based thermodynamic analysis (2007)
- Biomolecular Recognition of Glycosylated β3-Peptides by GalNAc Specific Lectins (2007)
- Investigation of beta-amino acids as building blocks in hepatitis c virus NS3 protease inhibitors (2007)
- Mechanistic studies of electrophilic protease inhibitors of full length hepatic C virus (HCV) NS3 (2007)
- Evaluation of a diverse set of potential P-1 carboxylic acid bioisosteres in hepatitis C virus NS3 protease inhibitors (2007)
- Evaluation of a diverse set of potential P1 carboxylic acid bioisosteres in hepatitis C virus NS3 protease inhibitors (2007)
- Phenylglycine as a Novel P2 Scaffold in Hepatitis C Virus NS3 Protease Inhibitors (2007)
- Biosensor-based screening and characterization of HIV-1 inhibitor interactions with Sap1, Sap2 and Sap3 from Candida albicans (2006)
- Biosensor-based kinetic characterization of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors (2006)
- Interaction kinetic characterization of HIV-1 reverse transcriptase non-nucleoside inhibitor resistance (2006)
- Characterization of Ca2+ interactions with matrix metallopeptidase-12 (2006)
- Sensitivity analysis and error structure of progress curves (2006)
- Detection of competitive enzyme inhibition with end point progress curve data (2006)
- Exploration of acyl sulfonamides as carboxylic acid replacements in protease inhibitors of the hepatitis C virus full-length NS3 (2006)
- Inhibition of viral proteases by Zingiberaceae extracts and flavones isolated from Kaempferia parviflora (2006)
- Early absorption and distribution analysis of antitumor and anti-AIDS drugs (2005)
- Refolding of the full-length non-structural protein 3 of hepatitis C virus (2005)
- Studies of substrate-induced conformational changes in human cytomegalovirus protease using optical biosensor technology (2004)
- Optimisation of peptide-based inhibitors of full-length hepatitis C virus NS3 protease (2004)
- Structure-activity relationships for the selectivity of hepatitis C virus NS3 protease inhibitors (2004)
- Kinetic and thermodynamic characterization of HIV-1 protease inhibitors (2004)
- Improved structure-activity relationship analysis of HIV-1 protease inhibitors using interaction kinetic data (2004)
- Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors (2003)
- Kinetic and mechanistic analysis of the association and dissociation of inhibitors interacting with secreted aspartic acid proteases 1 and 2 from Candida albicans (2003)
- Candida albicans secreted aspartic peptidase specificity (2003)
- Analysis of the pH-dependencies of the association and dissociation kinetics of HIV-1 protease inhibitors (2003)
- Acyl sulfonamides as potent protease inhibitors of the hepatitis C virus full-length NS3 (protease-helicase/NTPase) (2003)
- Refolding of a recombinant full-length non-structural (NS3) protein from hepatitis C virus by chromatographic procedures (2003)
- Peptide-based inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase): model compounds towards small molecule inhibitors (2003)
- Elucidation of HIV-1 protease resistance by characterization of interaction kinetics between inhibitors and enzyme variants (2003)
- Resistance profiles of cyclic and linear inhibitors of HIV-1 protease (2002)
- HIV-1 Vif-derived peptide inhibits drug-resistant HIV proteases (2002)
- Tetrapeptides as potent protease inhibitors of Hepatitis C Virus full-length NS3 (protease-helicase/NTPase) (2002)
- Peptide-based protease inhibitors of the hepatitis C virus full-length NS3 protein (protease-helicase/NTPase) (2002)
- Relationships between structure and interaction kinetics for HIV-1 protease inhibitors (2002)
- Expression and purification of recombinant full-length NS3 protease-helicase from a new variant of Hepatitis C virus (2002)
- P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays (2001)
- Inhibition of hepatitis C virus NS3 protease activity by product-based peptides is dependent on helicase domain (2001)
- Determination of interaction kinetic constants for HIV-1 protease inhibitors using optical biosensor technology (2001)
- Synthesis and comperative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors (2001)
- Capture and analysis of low molecular weight ligands by surface plasmon resonance combined with mass spectrometry (2001)
- Characterization of a set of HIV-1 protease inhibitors using binding kinetics data from a biosensor-based screen (2000)
- Kinetic analysis of the interaction between HIV-1 protease and inhibitors using optical biosensor technology (2000)
- Design and fast synthesis of C-terminal duplicated potent C2-symmetric P1/P1'-modified HIV-1 protease inhibitors (1999)
- Probing the kinetic mechanism and coenzyme specificity of glutathione reductase from the cyanobacterium Anabaena PCC 7120 by redesign of the pyridine-nucleotide-binding site (1999)
- Inhibitors of the C(2)-symmetric HIV-1 protease: nonsymmetric binding of asymmetric cyclic sulfamide with ketoxime groups in the P2/P2' side chains (1999)
- Design and synthesis of new potent C2-symmetric HIV-1 protease inhibitors (1998)
- Cyclic urea and sulfamide-based inhibitors of HIV-1 protease: Changes in binding mode upon modifications in the P1/P1 side chain (1998)
- Investigation of an allosteric site of HIV-1 proteinase involved in inhibition by Cu2+ (1998)
- Cyclic 7-membered sulfamide HIV-1 protease inhibitors (1998)
- Screening of compounds interacting with HIV-1 proteinase using optical biosensor technology (1998)
- Development of a radiochemical cyclooxygenase-1 and 2 in vitro assay for identification of natural products as inhibitors of prostaglandin biosynthesis (1998)
- HIV-1 protease inhibitors based on acyclic carbohydrates (1998)
- A convenient synthesis of 1-(S)-[1'-(S)-(t-butyloxycarbonylamino)-2'-phenylethyl]oxirane (1997)
- Cyclic HIV-1 protease inhibitors derived from mannitol (1997)
- Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs (1997)
- Synthesis of enantiomerically pure cis and trans 2-aminocyclopentanecarboxylic acids. Use of proline replacements in potential HIV-protease inhibitors (1997)
- Synthesis of C-2 symmetric potential inhibitors of HIV-1 protease from D-mannitol (1996)
- Isothiocyanates as substrates for human glutathione transferases (1995)
- Specific interaction between HIV-1 proteinase and 5'-phosphate peptidomimetic derivatives of nucleoside analogues (1995)
- The use of 5'-phosphate derivatives of nucleoside analogs as inhibitors of HIV-1 replication (1995)
- Engineering of a metal coordinating site into human glutathione transferase M1-1 based on immobilized metal ion affinity chromatography of homologous rat enzymes (1994)
- High-yield purification of HIV-1 proteinase expressed by a synthetic gene in Escherichia coli (1991)
- Cooperative effect of fructose bisphosphate and glyceraldehyde-3-phosphate dehydrogenase on aldolase action (1990)
- Proteolytic cleavage of microtubule-associated proteins by retroviral proteinases (1990)
- Paradoxical inhibition of rat glutathione transferase 4-4 by indomethacin explained by substrate-inhibitor-enzyme complexes in a random-order sequential mechanism (1988)
- Glutathione transferases - structure and catalytic activity (1988)
- Relaxed thiol substrate specificity of glutathione transferase effected by a non-substrate glutathione derivative (1988)
- Structure-activity relationships of 4-hydroxyalkenals in the conjugation catalysed by mammalian glutathione transferases (1987)
- Expression of class-pi glutathione transferase in drug-resistant human-melanoma cells (1987)
- Kinetic independence of the subunits of cytosolic glutathione transferase from the rat (1985)
- STRUCTURAL DATA AND ENZYMATIC-PROPERTIES DEFINING 3 CLASSES OF MAMMALIAN CYTOSOLIC GLUTATHIONE TRANSFERASE (1985)
- 4-Hydroxyalk-2-enals are substrates for glutathione transferase (1985)
- Purification of major basic glutathione transferase isoenzymes from rat liver by use of affinity chromatography and fast protein liquid chromatofocusing (1985)
- Target Engagement-Mediated Amplification for Monitoring Drug-Target Interactions in Situ
- Substrate specificity and pH dependence of secreted aspartic proteases Sap1, Sap2 and Sap3 from Candida albicans
- Kinetic characterization of HCV NS3 inhibitors using an SPR biosensor
- Kinetic, mechanistic and chemodynamic characterisation of non-nucleoside hepatitis C virus NS5B polymerase inhibitors using SPR biosensor technology
- Thermodynamic analysis of non-nucleoside inhibitor binding to HIV-1 reverse transcriptase
- The high affinity of hydroxamate-based MMP-12 inhibitors is due to an inherently slow dissociation rate of the enzyme-inhibitor complex
- Inhibition of HIV-1 protease by Cu2+ occurs by a reversible allosteric mechanism involving His-69
- Identification of complexities in HIV-1 protease - ligand interactions using biosensor technology
- Initial evaluation of biotinylated bilayer disks as model membranes for biosensor analyses
- Discovery of the subsite specificity of Candida albicans Sap1 and Sap2 and the design of potent peptidomimetic inhibitors
- Efficient protein binders for the C-reactive protein from a designed chemically modified peptide library
Conferences
- Molecular Interaction Analysis for Discovery of Drugs Targeting Enzymes and for Resolving Biological Function (2015)
- MIV-170 (2008)
- Investigation of beta-amino acids as building blocks in hepatitis c virus NS3 protease inhibitors (2007)
- Novel C-terminal functionalities in hepatitis C virus NS3 protease inhibitors (2005)
- Optimisation of peptide-based inhibitors of full-length hepatitis C virus NS3 protease (2004)
