Imperial College London

DrAnnaBarnard

Faculty of Natural SciencesDepartment of Chemistry

Research Fellow (Sir Henry Dale Fellowship)
 
 
 
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Contact

 

+44 (0)20 7594 8551a.barnard Website

 
 
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Location

 

Office 301MMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

20 results found

Rueda-Zubiaurre A, Yahiya S, Fischer O, Hu X, Saunders C, Sharma S, Straschil U, Shen J, Tate EW, Delves M, Baum J, Barnard A, Fuchter MJet al., 2020, Structure-activity relationship studies of a novel class of transmission blocking antimalarials targeting male gametes., Journal of Medicinal Chemistry, Vol: 63, Pages: 2240-2262, ISSN: 0022-2623

Malaria is still a leading cause of mortality among children in the developing world, and despite the immense progress made in reducing the global burden, further efforts are needed if eradication is to be achieved. In this context, targeting transmission is widely recognized as a necessary intervention towards that goal. After carrying out a screen to discover new transmission-blocking agents, herein we report our medicinal chemistry efforts to study the potential of the most robust hit, DDD01035881, as a male-gamete targeted compound. We reveal key structural features for the activity of this series and identify analogues with greater potency and improved metabolic stability. We believe this study lays the groundwork for further development of this series as a transmission blocking agent.

Journal article

Flack T, Romain C, White A, Haycock P, Barnard Aet al., 2019, Design, synthesis and conformational analysis of oligobenzanilides as multi-facial alpha-helix mimetics, Organic Letters, Vol: 21, Pages: 4433-4438, ISSN: 1523-7052

The design, synthesis, and conformationalanalysis of an oligobenzanilide helix mimetic scaffold capableof simultaneous mimicry of two faces of an α-helix is reported.The synthetic methodology provides access to diversemonomer building blocks amenable to solid-phase assemblyin just four synthetic steps. The conformational flexibility ofmodel dimers was investigated using a combination of solidand solution state methodologies supplemented with DFTcalculations. The lack of noncovalent constraints allows forsignificant conformational plasticity in the scaffold, thuspermitting it to successfully mimic residues i, i+2, i+4, i+6, i+7, and i+9 of a canonical α-helix.

Journal article

Delves M, Miguel-Blanco C, Matthews H, Molina I, Ruecker A, Yahiya S, Straschil U, Abraham M, Leon-Diaz ML, Fischer O, Zubiaurre A, Brandt J, Cortes A, Barnard A, Fuchter M, Calderon F, Winzeler E, Sinden R, Herreros E, Gamo FJ, Baum Jet al., 2018, A high throughput screen for next-generation leads targeting malaria parasite transmission, Nature Communications, Vol: 9, ISSN: 2041-1723

Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes of action. Since only 0.2–1% of asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route to interrupt disease transmission and mitigate resistance selection. Here we present a high-throughput screen of gametogenesis against a ~70,000 compound diversity library, identifying seventeen drug-like molecules that target transmission. Hit molecules possess varied activity profiles including male-specific, dual acting male–female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4-yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo efficacy. Development of leads with modes of action focussed on the sexual stages of malaria parasite development provide a previously unexplored base from which future therapeutics can be developed, capable of preventing parasite transmission through the population.

Journal article

Arrata I, Barnard A, Tomlinson DC, Wilson AJet al., 2017, Interfacing native and non-native peptides: using Affimers to recognise α-helix mimicking foldamers, Chemical Communications, Vol: 53, Pages: 2834-2837, ISSN: 1359-7345

Selection methods are used to identify Affimers that recognise α-helix mimicking N-alkylated aromatic oligoamides thus demonstrating foldamer and natural α-amino acid codes are compatible.

Journal article

Azzarito V, Rowell P, Barnard A, Edwards TA, Macdonald A, Warriner SL, Wilson AJet al., 2016, Probing Protein Surfaces: QSAR Analysis with Helix Mimetics, Chembiochem, Vol: 17, Pages: 768-773, ISSN: 1439-7633

α-Helix-mediated protein–protein interactions (PPIs) are important targets for small-molecule inhibition; however, generic approaches to inhibitor design are in their infancy and would benefit from QSAR analyses to rationalise the noncovalent basis of molecular recognition by designed ligands. Using a helix mimetic based on an oligoamide scaffold, we have exploited the power of a modular synthesis to access compounds that can readily be used to understand the noncovalent determinants of hDM2 recognition by this series of cell-active p53/hDM2 inhibitors.

Journal article

Barnard A, Long K, Martin HL, Miles JA, Edwards TA, Tomlinson DC, Macdonald A, Wilson AJet al., 2015, Selective and potent proteomimetic inhibitors of intracellular protein–protein interactions, Angewandte Chemie - International Edition, Vol: 54, Pages: 2960-2965, ISSN: 1433-7851

Inhibition of protein–protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed “proteomimetics”, which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified.

Journal article

Barnard A, Miles JA, Burslem GM, Barker AM, Wilson AJet al., 2014, Multivalent helix mimetics for PPI-inhibition, Organic & Biomolecular Chemistry, Vol: 13, Pages: 258-264, ISSN: 1477-0539

The exploitation of multivalent ligands for the inhibition of protein–protein interactions has not yet been explored as a supramolecular design strategy. This is despite the fact that protein–protein interactions typically occur within the context of multi-protein complexes and frequently exploit avidity effects or co-operative binding interactions to achieve high affinity interactions. In this paper we describe preliminary studies on the use of a multivalent N-alkylated aromatic oligoamide helix mimetic for inhibition of p53/hDM2 and establish that protein dimerisation is promoted, rather than enhanced binding resulting from a higher effective concentration of the ligand.

Journal article

Barnard A, Posocco P, Fermeglia M, Tschiche A, Calderon M, Pricl S, Smith DKet al., 2014, Double-degradable responsive self-assembled multivalent arrays - temporary nanoscale recognition between dendrons and DNA, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 12, Pages: 446-455, ISSN: 1477-0520

Journal article

Tschiche A, Staedtler AM, Malhotra S, Bauer H, Boettcher C, Sharbati S, Calderon M, Koch M, Zollner TM, Barnard A, Smith DK, Einspanier R, Schmidt N, Haag Ret al., 2014, Polyglycerol-based amphiphilic dendrons as potential siRNA carriers for in vivo applications, JOURNAL OF MATERIALS CHEMISTRY B, Vol: 2, Pages: 2153-2167, ISSN: 2050-750X

Journal article

Barnard A, Long K, Yeo DJ, Miles JA, Azzarito V, Burslem GM, Prabhakaran P, Edwards TA, Wilson AJet al., 2014, Orthogonal functionalisation of alpha-helix mimetics, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 12, Pages: 6794-6799, ISSN: 1477-0520

Journal article

Prabhakaran P, Barnard A, Murphy NS, Kilner CA, Edwards TA, Wilson AJet al., 2013, Aromatic Oligoamide Foldamers with a "Wet Edge" as Inhibitors of the -Helix-Mediated p53-hDM2 Protein-Protein Interaction, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Vol: 2013, Pages: 3504-3512, ISSN: 1434-193X

Journal article

Bromfield SM, Barnard A, Posocco P, Fermeglia M, Pricl S, Smith DKet al., 2013, Mallard Blue: A High-Affinity Selective Heparin Sensor That Operates in Highly Competitive Media, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 135, Pages: 2911-2914, ISSN: 0002-7863

Journal article

Ottaviani MF, Cangiotti M, Fiorani L, Barnard A, Jones SP, Smith DKet al., 2012, Probing dendron structure and nanoscale self-assembly using computer-aided analysis of EPR spectra, NEW JOURNAL OF CHEMISTRY, Vol: 36, Pages: 469-476, ISSN: 1144-0546

Journal article

Barnard A, Smith DK, 2012, Self-Assembled Multivalency: Dynamic Ligand Arrays for High-Affinity Binding, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 51, Pages: 6572-6581, ISSN: 1433-7851

Journal article

Barnard A, Calderon M, Tschiche A, Haag R, Smith DKet al., 2012, Effects of a PEG additive on the biomolecular interactions of self-assembled dendron nanostructures, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 10, Pages: 8403-8409, ISSN: 1477-0520

Journal article

Barnard A, Posocco P, Pricl S, Calderon M, Haag R, Hwang ME, Shum VWT, Pack DW, Smith DKet al., 2011, Degradable Self-Assembling Dendrons for Gene Delivery: Experimental and Theoretical Insights into the Barriers to Cellular Uptake, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 133, Pages: 20288-20300, ISSN: 0002-7863

Journal article

Fischer W, Quadir MA, Barnard A, Smith DK, Haag Ret al., 2011, Controlled Release of DNA From Photoresponsive Hyperbranched Polyglycerols with Oligoamine Shells, MACROMOLECULAR BIOSCIENCE, Vol: 11, Pages: 1736-1746, ISSN: 1616-5187

Journal article

Rodrigo AC, Barnard A, Cooper J, Smith DKet al., 2011, Self-Assembling Ligands for Multivalent Nanoscale Heparin Binding, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 50, Pages: 4675-4679, ISSN: 1433-7851

Journal article

Posocco P, Pricl S, Jones S, Barnard A, Smith DKet al., 2010, Less is more - multiscale modelling of self-assembling multivalency and its impact on DNA binding and gene delivery, CHEMICAL SCIENCE, Vol: 1, Pages: 393-404, ISSN: 2041-6520

Journal article

Barnard A, Dickson SJ, Paterson MJ, Todd AM, Steed JWet al., 2009, Enantioselective lactate binding by chiral tripodal anion hosts derived from amino acids, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 7, Pages: 1554-1561, ISSN: 1477-0520

Journal article

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