Synthesis and chemical characterisation of target identification reagents based on an inhibitor of human cell invasion by the parasite Toxoplasma gondii.
The use of phenotype-based screens as an approach for identifying novel small molecule tools is reliant on successful protein target identification strategies. Here we report on the synthesis and chemical characterisation of a novel reagent for protein target identification based on a small molecule inhibitor of human cell invasion by the parasite Toxoplasma gondii. A detailed (1)H NMR study and biological testing confirmed that incorporation of an amino-containing functional group into the aryl ring of this inhibitor was possible without loss of biological activity. Interesting chemical reactivity differences were identified resulting from incorporation of the new substituent. The amine functionality was then used to prepare a biotinylated reagent that is central to our current protein target identification studies with this inhibitor.
Evans
Kathryn M
KM
School of Chemistry and Centre for Biomolecular Sciences, University of St Andrews, North Haugh, St Andrews, Fife, Scotland, UK, KY16 9ST.
Haraldsen
Jeralyn D
JD
Pearson
Russell J
RJ
Slawin
Alexandra M Z
AM
Ward
Gary E
GE
Westwood
Nicholas J
NJ
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism* / Q000469:parasitology; D003432:Cross-Linking Reagents / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity; D014122:Toxoplasma / Q000187:drug effects* / Q000502:physiology*
D000588:Amines; D000977:Antiparasitic Agents; D003432:Cross-Linking Reagents; D007202:Indicators and Reagents