Michael J. Hannon
University of Birmingham
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Featured researches published by Michael J. Hannon.
Chemical Society Reviews | 2007
Michael J. Hannon
Non-covalent DNA-recognition by synthetic agents is surveyed in this tutorial review, and contrasted with biomolecular DNA-recognition. The principles and forces involved in DNA recognition are similar to those seen elsewhere in the wider field of supramolecular chemistry, although the size, surface dimensions and nature of DNA introduce new possibilities and challenges. Recent discoveries of new binding motifs, and new biological structural and genomic information from bioscience, are affording new opportunities for supramolecular chemistry, where shape, fit and orientation play such an important role.
Supramolecular Chemistry | 2004
Michael J. Hannon; Laura J. Childs
The fascination of scientists, and particularly supramolecular chemists, with helical arrays continues unabated [1,2]. These structures have provided the playground in which many supramolecular des...
Pure and Applied Chemistry | 2007
Michael J. Hannon
The field of metal-based anticancer drugs was initiated by cisplatin, one of the leading agents in clinical use. Cisplatin acts by binding to DNA and forming 1,2 intrastrand cross-links. Its importance is reflected by the fact that it is estimated that 50-70 % of cancer patients are treated with a platinum drug [7]. For some time, molecular designs in the metallo-drug field remained obdurately anchored in cis-diamine platinum(II) chemistry, but now the field is evolving rapidly with a variety of alternate and very diverse designs being explored. These designs give rise to new spectra of activity and potency and can circumvent cisplatin resistance. This critical review considers the existing clinical platinum drugs, and those currently in commercial development, alongside the new designs including ruthenium anticancer and antimetastatic drugs in clinical trials, polynuclear drugs, organometallic drugs, titanium and gallium drugs, and emerging supramolecular metallo-drugs that act on DNA by noncovalent interactions. The rapid evolution of the field is being informed by post-genomic knowledge and approaches, and further dramatic step-change breakthroughs can be expected as a result; harnessing this knowledge and responding to and taking advantage of this new environment requires integration of chemistry and biology research.
Proceedings of the National Academy of Sciences of the United States of America | 2002
Isabelle Meistermann; Virtudes Moreno; María J. Prieto; Erlend Moldrheim; Einar Sletten; Syma Khalid; P. Mark Rodger; Jemma C. Peberdy; Christian J. Isaac; Alison Rodger; Michael J. Hannon
We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major groove of DNA with a binding constant in excess of 107 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.
Proceedings of the National Academy of Sciences of the United States of America | 2011
Vera K. Schoft; Nina Chumak; Yeonhee Choi; Michael J. Hannon; Marcelina García-Aguilar; Adriana Machlicova; Lucyna Slusarz; Magdalena Mosiolek; Jin-Sup Park; Guen Tae Park; Robert L. Fischer; Hisashi Tamaru
In double fertilization, the vegetative cell of the male gametophyte (pollen) germinates and forms a pollen tube that brings to the female gametophyte two sperm cells that fertilize the egg and central cell to form the embryo and endosperm, respectively. The 5-methylcytosine DNA glycosylase DEMETER (DME), expressed in the central cell, is required for maternal allele demethylation and gene imprinting in the endosperm. By contrast, little is known about the function of DME in the male gametophyte. Here we show that reduced transmission of the paternal mutant dme allele in certain ecotypes reflects, at least in part, defective pollen germination. DME RNA is detected in pollen, but not in isolated sperm cells, suggesting that DME is expressed in the vegetative cell. Bisulfite sequencing experiments show that imprinted genes (MEA and FWA) and a repetitive element (Mu1a) are hypomethylated in the vegetative cell genome compared with the sperm genome, which is a process that requires DME. Moreover, we show that MEA and FWA RNA are detectable in pollen, but not in isolated sperm cells, suggesting that their expression occurs primarily in the vegetative cell. These results suggest that DME is active and demethylates similar genes and transposons in the genomes of the vegetative and central cells in the male and female gametophytes, respectively. Although the genome of the vegetative cell does not participate in double fertilization, its DME-mediated demethylation is important for male fertility and may contribute to the reconfiguration of the methylation landscape that occurs in the vegetative cell genome.
Angewandte Chemie | 1999
Michael J. Hannon; Siona Bunce; Adam J. Clarke; Nathaniel W. Alcock
Careful selection of the spacer group used to separate the metal-binding domains allows control of the directionality in a helix; self-assembly leads uniquely to a double-helical cation with a head-to-tail (HT) configuration (shown schematically) in both the solid state and solution.
Journal of Biological Inorganic Chemistry | 2009
Eva Corral; Anna C. G. Hotze; Æ Hans den Dulk; Anna Leczkowska; Alison Rodger; Michael J. Hannon; Jan Reedijk
Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L1L2](2−n)+, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{μ-H2N(CH2)6NH2}]4+. The ligand tpy is 2,2′:6′,2″-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,2′-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl−, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.
Polyhedron | 1992
Edwin C. Constable; Michael J. Hannon; Avelino Martín; Paul R. Raithby; Derek A. Tocher
Abstract 2,2′:6′,2″:6″,2‴-Quaterpyridine (qtpy) forms double-helical binuclear complexes with metal ions adopting a pseudo-tetrahedral geometry; it is not necessary to design a sterically constrained ligand for this purpose, as the crystal structures of [Cu2(qtpy)2][PF6]2 and [Ag2 (qtpy)2][BF4]2 demonstrate; the role of the substituents is not to control the assembly of the helix, but to control its pitch.
Journal of The Chemical Society-dalton Transactions | 1996
Edwin C. Constable; Susan M. Elder; Michael J. Hannon; Avelino Martín; Paul R. Raithby; Derek A. Tocher
The co-ordination behaviour of 2,2′ : 6′,2″ : 6″,2‴-quaterpyridine (qtpy) has been systematically studied. Double-helical dinuclear complexes were only obtained with ions bearing a low charge or a low charge-to-radius ratio and which have no electronically imposed preference for geometries in which the ligand can present a planar donor set. The double-helical complexes [Cu2(qtpy)2][PF6]2 and [Ag2(qtpy)2][BF4]2 have been structurally characterised, as have the mononuclear species [Ni(qtpy)(OH2)2][BF4]2 and [Pd(qtpy)][PF6]2. Complexes with zinc(II) and cadmium(II) are mononuclear but it is suggested that a double-helical dinuclear complex is formed with mercury(II).
Inorganica Chimica Acta | 1993
Edwin C. Constable; Michael J. Hannon
Abstract The reaction of [Ru(tpy)Cl 3 ] with the potentially cyclometallating ligand 6-phenyl-2,2′-bipyridine (HL) has been examined in a variety of solvents. In glacial acetic acid the ligand acts as a substituted 2,2′-bipyridine and reacts to give the complex cation [Ru(tpy)(HL)CL] + , containing a bidentate N,N′-bonded HL ligand. The structure of this complex has been unambiguously established from its 1 H NMR spectrum. In contrast, the use of water as a solvent gives the cyclometallated complex cation [Ru(tpy)(L)] + . In methanol and butan-1-ol, mixtures of these two products are formed. The work has been extended to 2,2′:6′,2″-terpyridines with aromatic substituents in the 4′ position and the complexes have been characterised by 1 H NMR, electronic and FAB mass spectroscopic techniques and also by cyclic voltammetry.