Development of a Photo-Cross-Linkable Diaminoquinazoline Inhibitor for Target Identification in Plasmodium falciparum.
ACS Infect Dis
; 4(4): 523-530, 2018 04 13.
Article
em En
| MEDLINE
| ID: mdl-29377668
ABSTRACT
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 similarities between the target profiles of the probe and the representative diaminoquinazoline BIX-01294. Initial pull-down proteomics experiments identified 104 proteins from different classes, many of which are essential, highlighting the suitability of the developed probe as a valuable tool for target identification in Plasmodium falciparum.
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Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Reagentes de Ligações Cruzadas
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Inibidores Enzimáticos
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Antimaláricos
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
ACS Infect Dis
Ano de publicação:
2018
Tipo de documento:
Article