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Plasmodium gametocyte inhibition identified from a natural-product-based fragment library.
- Source :
-
ACS chemical biology [ACS Chem Biol] 2013 Dec 20; Vol. 8 (12), pp. 2654-9. Date of Electronic Publication: 2013 Oct 03. - Publication Year :
- 2013
-
Abstract
- Fragment-based screening is commonly used to identify compounds with relatively weak but efficient localized binding to protein surfaces. We used mass spectrometry to study fragment-sized three-dimensional natural products. We identified seven securinine-related compounds binding to Plasmodium falciparum 2'-deoxyuridine 5'-triphosphate nucleotidohydrolase (PfdUTPase). Securinine bound allosterically to PfdUTPase, enhancing enzyme activity and inhibiting viability of both P. falciparum gametocyte (sexual) and blood (asexual) stage parasites. Our results provide a new insight into mechanisms that may be applicable to transmission-blocking agents.
- Subjects :
- Alkaloids chemistry
Alkaloids isolation & purification
Alkaloids pharmacology
Antimalarials chemistry
Antimalarials isolation & purification
Azepines chemistry
Azepines isolation & purification
Azepines pharmacology
Deoxyuracil Nucleotides antagonists & inhibitors
Deoxyuracil Nucleotides chemistry
Deoxyuracil Nucleotides metabolism
Dose-Response Relationship, Drug
Heterocyclic Compounds, Bridged-Ring chemistry
Heterocyclic Compounds, Bridged-Ring isolation & purification
Heterocyclic Compounds, Bridged-Ring pharmacology
Kinetics
Lactones chemistry
Lactones isolation & purification
Lactones pharmacology
Life Cycle Stages physiology
Piperidines chemistry
Piperidines isolation & purification
Piperidines pharmacology
Plasmodium falciparum enzymology
Plasmodium falciparum growth & development
Protozoan Proteins chemistry
Protozoan Proteins metabolism
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins metabolism
Spectrometry, Mass, Electrospray Ionization
Structure-Activity Relationship
Antimalarials pharmacology
Biological Products chemistry
Life Cycle Stages drug effects
Plasmodium falciparum drug effects
Protozoan Proteins antagonists & inhibitors
Small Molecule Libraries chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1554-8937
- Volume :
- 8
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- ACS chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 24079418
- Full Text :
- https://doi.org/10.1021/cb400582b