Proteomics

Dataset Information

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Use of a Photo-crosslinkable Diaminoquinazoline Inhibitor for Target Identification in Plasmodium Falciparum

ABSTRACT: Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors (BIX-01294). Despite this, robust evidence for their molecular targets, proteome-wide, is lacking. Here we report the design and development of a small-molecule photo-crosslinkable probe to investigate the targets of our diaminoquinazoline series. We demonstrate the effectiveness of our designed probe for photoaffinity labelling of Plasmodium lysates and initial pull-down proteomics experiments identified proteins from different classes enriched by the probe, highlighting the suitability of the developed probe as a valuable tool for protein identification in Plasmodium falciparum.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Plasmodium Falciparum (isolate 3d7)

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Alexandra Lubin  

LAB HEAD: Dr Matthew Fuchter

PROVIDER: PXD008164 | Pride | 2018-02-16

REPOSITORIES: Pride

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Dataset's files

Source:
Action DRS
Controlsamplereplicate1AL_C_1.raw Raw
Controlsamplereplicate2AL_C_3.raw Raw
Plasmodiumprobepull-downtxt.zip Other
Probesamplereplicate1AL_P4_1.raw Raw
Probesamplereplicate2AL_P4_3.raw Raw
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Publications

Development of a Photo-Cross-Linkable Diaminoquinazoline Inhibitor for Target Identification in Plasmodium falciparum.

Lubin Alexandra S AS   Rueda-Zubiaurre Ainoa A   Matthews Holly H   Baumann Hella H   Fisher Fabio R FR   Morales-Sanfrutos Julia J   Hadavizadeh Kate S KS   Nardella Flore F   Tate Edward W EW   Baum Jake J   Scherf Artur A   Fuchter Matthew J MJ  

ACS infectious diseases 20180205 4

Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors. Despite this, robust evidence for their molecular targets is lacking. Here we report the design and development of a small-molecule photo-cross-linkable probe to investigate the targets of our diaminoquinazoline series. We demonstrate the effectiveness of our designed probe for photoaffinity labeling of Plasmodium lysates and identify s  ...[more]

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