Alison Rodger - Academia.edu (original) (raw)
Papers by Alison Rodger
Encyclopedia of Biophysics, 2013
Proton-pumping NADH-ubiquinone oxidoreductase (complex I) is a very large membrane protein comple... more Proton-pumping NADH-ubiquinone oxidoreductase (complex I) is a very large membrane protein complex that is found in many bacteria and almost all eukaryotes (Brandt 2006). In the mitochondrial respiratory chain it couples the transfer of two electrons from NADH to ubiquinone to the vectorial translocation of four protons across the inner membrane of the organelle and thereby generates up to 40% of the driving force for ATP synthesis by ATP synthase. Complex I is a source of reactive oxygen species and is involved in the pathogenesis of encephalomyopathies and neurodegenerative diseases.
Encyclopedia of Biophysics, 2013
Calcium Activation of K + Channels: RCK Domains, Fig. 3 Calcium-and Mg 2+-binding sites in BK RCK... more Calcium Activation of K + Channels: RCK Domains, Fig. 3 Calcium-and Mg 2+-binding sites in BK RCK1 domain. (a) Structural details of the BK high-affinity Ca 2+-binding site. Histine 365 appears to be involved in a pH-dependent activation of BK channels. Upon protonation this residue interacts electrostatically with D367 mimicking the effect of Ca 2+. It is unclear whether M513 binds Ca 2+ directly or if it is important in maintaining the Ca 2+-binding site structure. (b) Low-affinity Ca 2+-and Mg 2+-binding sites, located on the upper plateau of the gating ring and very near the membrane surface (Wu et al. 2010)
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
Proceedings of the National Academy of Sciences of the United States of America, Apr 16, 2002
We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major... more We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major groove of DNA with a binding constant in excess of 10 7 M ؊1 and induces DNA bending and intramolecular coiling. The two enantiomers of the helical molecule bind differently to DNA and have different structural effects. We report the characterization of the interactions by a range of biophysical techniques. The M helical cylinder binds to the major groove and induces dramatic intramolecular coiling. The DNA bending is less dramatic for the P enantiomer.
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
Encyclopedia of Analytical Chemistry, Jan 13, 2014
Contents 1 Spectroscopy, chirality, and oriented Systems 1.1 Introduction 1 1.2 Electromagnetic r... more Contents 1 Spectroscopy, chirality, and oriented Systems 1.1 Introduction 1 1.2 Electromagnetic radiation and spectroscopy 2 1.3 Measuring a CD spectrum 6 1.4 Design and implementation of an LD experiment 8 References 14
Spectroscopy, chirality, and oriented systems Circular dichroism of biomolecules Linear dichroism... more Spectroscopy, chirality, and oriented systems Circular dichroism of biomolecules Linear dichroism of biomolecules Linear dichroism of small molecules Analysis of circular dichroism: electric dipole allowed transitions Analysis of circular dichroism: magnetic dipole allowed transitions and magnetic CD Circular dichroism formalism Appendices
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Lancet, 2021
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Articles
All biological processes are fundamentally inter-molecular interactions. In order to understand, ... more All biological processes are fundamentally inter-molecular interactions. In order to understand, and hence control, biomolecule structure and function, methods are required that probe biological systems at the molecular level, ideally with those molecules being in their native environment. The research summarized herein has at its core the development and application of ultra violet (UV)-visible spectrophotometric techniques for this purpose, in particular circular dichroism (CD) and linear dichroism (LD) but also absorbance, fluorescence and resonance light scattering. The spectroscopy is complemented by fundamental theoretical work on molecular structure and reactivity that forms the basis for designing molecules to bind to biomolecules for a particular structural or functional effect. A brief summary of the contributions of the listed publications to our understanding of 'Molecular aspects of biomolecule structure and function' is given below under five headings: Circular dichroism theory Molecular geometry and reactivity Small molecule-macromolecule interactions: spectroscopic probes of inter-molecular geometries Molecular design for nucleic acid structure and control Spectroscopic probes of biomolecule structure: instrumentation and application In general terms these correspond to successive phases of the research programme, however, all areas have been present since the first publications in 1983 and can be traced weaving through all subsequent activity.
Chemical Science, 2013
Enantiomers of a relatively rigid DNA-binding metallo-helix are shown to have comparable activity... more Enantiomers of a relatively rigid DNA-binding metallo-helix are shown to have comparable activity to that of cisplatin against the cell lines MCF7 (human breast adenocarcinoma) and A2780 (human ovarian carcinoma) but are ca five times more active against the cisplatin-resistant A2780cis. The cell-line HCT116 p53 +/+ (human colon carcinoma) is highly sensitive giving IC 50 values in the nM range, far lower than the cisplatin control. The hypothesis that the biological target of such metallohelices is DNA is probed by various techniques. Tertiary structure changes in ct-DNA (formation of loops and intramolecular coiling) on exposure to the compounds are demonstrated by atomic force microscopy and supported by circular/linear dichroism in solution. Selectivity for 5 0-CACATA and 5 0-CACTAT segments is shown by DNase I footprinting. Various three-and four-way oligonucleotide junctions are stabilised, and remarkably only the L metallo-helix enantiomer stabilizes T-shaped 3WJs during gel electrophoresis; this is despite the lack of a known helix binding site. In studies with oligonucleotide duplexes with bulges it is also shown for the first time that the metallo-helix binding strength and the number of binding sites are dependent on the size of the bulge. In contrast to all the above, flexible metallo-helices show little propensity for structured or selective DNA binding, and while for A2780 the cancer cell line cytotoxicity is retained the A2780cis strain shows significant resistance. For all compounds in the study, H2AX FACS assays on HCT116 p53 +/+ showed that no significant DNA damage occurs. In contrast, cell cycle analysis shows that the DNA binders arrest cells in the G2/mitosis phase, and while all compounds cause apoptosis, the DNA binders have the greater effect. Taken together these screening and mechanistic results are consistent with the more rigid helices acting via a DNA binding mechanism while the flexible assemblies do not.
Physical Chemistry Chemical Physics, 2006
Encyclopedia of Biophysics, 2013
Proton-pumping NADH-ubiquinone oxidoreductase (complex I) is a very large membrane protein comple... more Proton-pumping NADH-ubiquinone oxidoreductase (complex I) is a very large membrane protein complex that is found in many bacteria and almost all eukaryotes (Brandt 2006). In the mitochondrial respiratory chain it couples the transfer of two electrons from NADH to ubiquinone to the vectorial translocation of four protons across the inner membrane of the organelle and thereby generates up to 40% of the driving force for ATP synthesis by ATP synthase. Complex I is a source of reactive oxygen species and is involved in the pathogenesis of encephalomyopathies and neurodegenerative diseases.
Encyclopedia of Biophysics, 2013
Calcium Activation of K + Channels: RCK Domains, Fig. 3 Calcium-and Mg 2+-binding sites in BK RCK... more Calcium Activation of K + Channels: RCK Domains, Fig. 3 Calcium-and Mg 2+-binding sites in BK RCK1 domain. (a) Structural details of the BK high-affinity Ca 2+-binding site. Histine 365 appears to be involved in a pH-dependent activation of BK channels. Upon protonation this residue interacts electrostatically with D367 mimicking the effect of Ca 2+. It is unclear whether M513 binds Ca 2+ directly or if it is important in maintaining the Ca 2+-binding site structure. (b) Low-affinity Ca 2+-and Mg 2+-binding sites, located on the upper plateau of the gating ring and very near the membrane surface (Wu et al. 2010)
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
Proceedings of the National Academy of Sciences of the United States of America, Apr 16, 2002
We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major... more We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major groove of DNA with a binding constant in excess of 10 7 M ؊1 and induces DNA bending and intramolecular coiling. The two enantiomers of the helical molecule bind differently to DNA and have different structural effects. We report the characterization of the interactions by a range of biophysical techniques. The M helical cylinder binds to the major groove and induces dramatic intramolecular coiling. The DNA bending is less dramatic for the P enantiomer.
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
Encyclopedia of Analytical Chemistry, Jan 13, 2014
Contents 1 Spectroscopy, chirality, and oriented Systems 1.1 Introduction 1 1.2 Electromagnetic r... more Contents 1 Spectroscopy, chirality, and oriented Systems 1.1 Introduction 1 1.2 Electromagnetic radiation and spectroscopy 2 1.3 Measuring a CD spectrum 6 1.4 Design and implementation of an LD experiment 8 References 14
Spectroscopy, chirality, and oriented systems Circular dichroism of biomolecules Linear dichroism... more Spectroscopy, chirality, and oriented systems Circular dichroism of biomolecules Linear dichroism of biomolecules Linear dichroism of small molecules Analysis of circular dichroism: electric dipole allowed transitions Analysis of circular dichroism: magnetic dipole allowed transitions and magnetic CD Circular dichroism formalism Appendices
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Royal Society of Chemistry eBooks, Sep 2, 2010
The Lancet, 2021
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Articles
All biological processes are fundamentally inter-molecular interactions. In order to understand, ... more All biological processes are fundamentally inter-molecular interactions. In order to understand, and hence control, biomolecule structure and function, methods are required that probe biological systems at the molecular level, ideally with those molecules being in their native environment. The research summarized herein has at its core the development and application of ultra violet (UV)-visible spectrophotometric techniques for this purpose, in particular circular dichroism (CD) and linear dichroism (LD) but also absorbance, fluorescence and resonance light scattering. The spectroscopy is complemented by fundamental theoretical work on molecular structure and reactivity that forms the basis for designing molecules to bind to biomolecules for a particular structural or functional effect. A brief summary of the contributions of the listed publications to our understanding of 'Molecular aspects of biomolecule structure and function' is given below under five headings: Circular dichroism theory Molecular geometry and reactivity Small molecule-macromolecule interactions: spectroscopic probes of inter-molecular geometries Molecular design for nucleic acid structure and control Spectroscopic probes of biomolecule structure: instrumentation and application In general terms these correspond to successive phases of the research programme, however, all areas have been present since the first publications in 1983 and can be traced weaving through all subsequent activity.
Chemical Science, 2013
Enantiomers of a relatively rigid DNA-binding metallo-helix are shown to have comparable activity... more Enantiomers of a relatively rigid DNA-binding metallo-helix are shown to have comparable activity to that of cisplatin against the cell lines MCF7 (human breast adenocarcinoma) and A2780 (human ovarian carcinoma) but are ca five times more active against the cisplatin-resistant A2780cis. The cell-line HCT116 p53 +/+ (human colon carcinoma) is highly sensitive giving IC 50 values in the nM range, far lower than the cisplatin control. The hypothesis that the biological target of such metallohelices is DNA is probed by various techniques. Tertiary structure changes in ct-DNA (formation of loops and intramolecular coiling) on exposure to the compounds are demonstrated by atomic force microscopy and supported by circular/linear dichroism in solution. Selectivity for 5 0-CACATA and 5 0-CACTAT segments is shown by DNase I footprinting. Various three-and four-way oligonucleotide junctions are stabilised, and remarkably only the L metallo-helix enantiomer stabilizes T-shaped 3WJs during gel electrophoresis; this is despite the lack of a known helix binding site. In studies with oligonucleotide duplexes with bulges it is also shown for the first time that the metallo-helix binding strength and the number of binding sites are dependent on the size of the bulge. In contrast to all the above, flexible metallo-helices show little propensity for structured or selective DNA binding, and while for A2780 the cancer cell line cytotoxicity is retained the A2780cis strain shows significant resistance. For all compounds in the study, H2AX FACS assays on HCT116 p53 +/+ showed that no significant DNA damage occurs. In contrast, cell cycle analysis shows that the DNA binders arrest cells in the G2/mitosis phase, and while all compounds cause apoptosis, the DNA binders have the greater effect. Taken together these screening and mechanistic results are consistent with the more rigid helices acting via a DNA binding mechanism while the flexible assemblies do not.
Physical Chemistry Chemical Physics, 2006