Characterization of Platinum Anticancer Drug Protein-Binding Sites Using a Top-Down Mass Spectrometric Approach

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Crosslinking Allosteric Sites on the Nucleosome Core Particle

Lucinda Kate Batchelor

Designing compounds that bind to the acidic patch of the nucleosome core particle (NCP) is an emerging therapeutic approach that can inhibit the binding of key chromatin factors. Pretreatment of human ovarian carcinoma, A2780, cells with RAPTA-T, an antime ...

EPFL2019

Mechanics of Allostery: Contrasting the Induced Fit and Population Shift Scenarios

Matthieu Wyart, Stefano Zamuner, Riccardo Ravasio, Solange Marie Flatt

In allosteric proteins, binding a ligand can affect function at a distant location, for example, by changing the binding affinity of a substrate at the active site. The induced fit and population shift models, which differ by the assumed number of stable c ...

CELL PRESS2019

Exploring on Protein-DNA interactions

Alexandra Styliani Kalantzi

A variety of DNA-binding proteins organizes the chromosomal DNA and regulates gene transcription, and DNA replication and recombination. In particular, for gene regulation there is a category of DNA-binding proteins, the transcription factors, which can de ...

EPFL2019

Screening-based approach to discover effective platinum-based chemotherapies for cancers with poor prognosis

Paul Joseph Dyson, Gerardo Turcatti, Fabien Kuttler, Damiano Banfi, Hristo Plamenov Varbanov

Drug combinations are extensively used to treat cancer and are often selected according to complementary mechanisms. Here, we describe a cell-based high-throughput screening assay for identification of synergistic combinations between broadly applied plati ...

2019

Allosteric Protein Switches based on Antibody Mimetics

Helen Rebecca Ostlund Farrants

Synthetic protein switches are proteins that can be controlled by an external input, and are useful tools to probe protein function. Antibody fragments and antibody mimetics can be selected to bind, activate, or inhibit several diverse protein targets. Nev ...

EPFL2019

Bond-selective and surface-site-specific dissociation of methane on platinum

Ana Gutiérrez González

I present a molecular beam study of methane dissociation on differ-ent surface sites of several platinum single crystal surfaces (Pt(111), Pt(211), Pt(210), Pt(110)-(2x1)). The experiments were performed in a molecular beam/surface-science apparatus that c ...

EPFL2019

alpha-Diimine homologues of cisplatin: synthesis, speciation in DMSO/water and cytotoxicity

Paul Joseph Dyson, Lucinda Kate Batchelor

The Pt(ii) -diimine complexes [PtCl2{N-2-(HCNR)(2)}] (R = C6H11, 1; 4-C6H10OH, 2; 4-C6H4CH3, 3; 4-C6H4OH, 4) and [PtCl2{N-2-(CH3CNOH)(2)}] (5) were prepared in 60-81% yields from the 1:1 molar reactions of cis-[PtCl2(DMSO)(2)] with the appropriate -diimine ...

ROYAL SOC CHEMISTRY2018

Rosetta FunFolDes - A general framework for the computational design of functional proteins

Bruno Emanuel Ferreira De Sousa Correia, Jaume Bonet Martinez, Stéphane Rosset, Fabian Sesterhenn, Andreas Scheck, Sarah Wehrle, Che Yang, Freyr Sverrisson, Sabrina Susan Vollers, Mélanie Evelyne Villard

The robust computational design of functional proteins has the potential to deeply impact translational research and broaden our understanding of the determinants of protein function and stability. The low success rates of computational design protocols an ...

2018

Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding

Hilal Lashuel, Juan Kiwi, Bruno Claude Daniel Fauvet, Anass Chiki

Intracellular deposits of α-synuclein in the form of Lewy bodies are major hallmarks of Parkinson’s disease (PD) and a range of related neurodegenerative disorders. Post-translational modifications (PTMs) of α-synuclein are increasingly thought to be major ...

2018

The mechanism of tumour cell death by metal-based anticancer drugs is not only a matter of DNA interactions

Paul Joseph Dyson

Platinum drugs are extensively used in the clinic to treat cancer, often leading to a palliative response rather than a cure. While DNA is considered to be the primary target of platinum drugs, there is no clear relationship between cellular platinum accum ...

2018