Skip to main content
Home
Department Of Physics text logo
  • Research
    • Our research
    • Our research groups
    • Our research in action
    • Research funding support
    • Summer internships for undergraduates
  • Study
    • Undergraduates
    • Postgraduates
  • Engage
    • For alumni
    • For business
    • For schools
    • For the public
Menu
Department of Physics
Credit: Jack Hobhouse

Dr Hannah Lingard

Head of Research Facilitation

Sub department

  • Professional and support services
hannah.lingard@physics.ox.ac.uk
Telephone: 01865 (2)83137
Denys Wilkinson Building, room 654
  • About
  • Publications

Promiscuous targeting of bromodomains by Bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia

Science Advances American Association for the Advancement of Science 2:10 (2016) e1600760

Authors:

Sarah Picaud, Katharina Leonards, Jean-Philippe Lambert, Oliver Dovey, Christopher Wells, Oleg Fedorov, Octovia Monteiro, Takao Fujisawa, Chen-Yi Wang, Hannah Lingard, Cynthia Tallant, Nikzad Nikbin, Lucie Guetzoyan, Richard Ingham, Steven V Ley, Paul Brennan, Susanne Muller, Anastasia Samsonova, Anne-Claude Gingras, Juerg Schwaller, George Vassiliou, Stefan Knapp, Panagiotis Filippakopoulos

Abstract:

Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET inhibitors and their significant activity in diverse tumor models has rapidly translated into clinical studies and has motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of bromodomain protein complexes complicates predictions of consequences of their pharmacological targeting. To address this issue we developed a promiscuous bromodomain inhibitor (bromosporine, BSP) that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle we studied the effect of BSP in leukemic cell-lines known to be sensitive to BET inhibition and found as expected strong anti-proliferative activity. Comparison of the modulation of transcriptional profiles by BSP at short inhibitor exposure resulted in a BET inhibitor signature but no significant additional changes in transcription that could account for inhibition of other BRDs. Thus, non-selective targeting of BRDs identified BETs, but not other BRDs, as master regulators of a context dependent primary transcription response.
More details from the publisher
Details from ORA
More details
More details

A Lewis acid-mediated conformational switch.

Organic & biomolecular chemistry 12:40 (2014) 7937-7941

Authors:

Peter C Knipe, Hannah Lingard, Ian M Jones, Sam Thompson, Andrew D Hamilton

Abstract:

Molecules that change conformation in response to a stimulus have numerous uses, such as artificial chemoreceptors, novel drug delivery strategies and liquid crystal technology. Here we describe the design, synthesis and conformational behaviour of an isonicotinamide-substituted diphenylacetylene upon recognition of Lewis acids, including metalloporphyrins. Binding of these at a remote site - the pyridyl nitrogen - increases hydrogen-bond donor ability of the proximal amide NH, causing an increased preference for the alkyne rotamer in which this hydrogen bond is maintained.
More details from the publisher
More details
More details

Selective Targeting of Protein Interactions Mediated by BET Bromodomains

Chapter in Concepts and Case Studies in Chemical Biology, Wiley (2014) 295-308

Authors:

Susanne Müller, Hannah Lingard, Stefan Knapp
More details
More details from the publisher

Diphenylacetylene-linked peptide strands induce bidirectional β-sheet formation.

Angewandte Chemie (International ed. in English) 53:14 (2014) 3650-3653

Authors:

Hannah Lingard, Jeongmin T Han, Amber L Thompson, Ivanhoe KH Leung, Richard TW Scott, Sam Thompson, Andrew D Hamilton

Abstract:

In the search for synthetic mimics of protein secondary structures relevant to the mediation of protein-protein interactions, we have synthesized a series of tetrasubstituted diphenylacetylenes that display β-sheet structures in two directions. Extensive X-ray crystallographic and NMR solution phase studies are consistent with these proteomimetics adopting sheet structures, displaying both hydrophobic and hydrophilic amino acid side chains.
More details from the publisher
More details
More details

[1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains.

Journal of medicinal chemistry 57:2 (2014) 462-476

Authors:

Oleg Fedorov, Hannah Lingard, Chris Wells, Octovia P Monteiro, Sarah Picaud, Tracy Keates, Clarence Yapp, Martin Philpott, Sarah J Martin, Ildiko Felletar, Brian D Marsden, Panagis Filippakopoulos, Susanne Müller, Stefan Knapp, Paul E Brennan

Abstract:

Bromodomains are gaining increasing interest as drug targets. Commercially sourced and de novo synthesized substituted [1,2,4]triazolo[4,3-a]phthalazines are potent inhibitors of both the BET bromodomains such as BRD4 as well as bromodomains outside the BET family such as BRD9, CECR2, and CREBBP. This new series of compounds is the first example of submicromolar inhibitors of bromodomains outside the BET subfamily. Representative compounds are active in cells exhibiting potent cellular inhibition activity in a FRAP model of CREBBP and chromatin association. The compounds described are valuable starting points for discovery of selective bromodomain inhibitors and inhibitors with mixed bromodomain pharmacology.
More details from the publisher
More details
More details

Pagination

  • Current page 1
  • Page 2
  • Page 3
  • Next page Next
  • Last page Last

Footer Menu

  • Contact us
  • Giving to the Dept of Physics
  • Work with us
  • Media

User account menu

  • Log in

Follow us

FIND US

Clarendon Laboratory,

Parks Road,

Oxford,

OX1 3PU

CONTACT US

Tel: +44(0)1865272200

University of Oxfrod logo Department Of Physics text logo
IOP Juno Champion logo Athena Swan Silver Award logo

© University of Oxford - Department of Physics

Cookies | Privacy policy | Accessibility statement

Built by: Versantus

  • Home
  • Research
  • Study
  • Engage
  • Our people
  • News & Comment
  • Events
  • Our facilities & services
  • About us
  • Current students
  • Staff intranet