{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST001239","ANALYSIS_ID":"AN002058","VERSION":"1","CREATED_ON":"August 13, 2019, 4:44 pm"},

"PROJECT":{"PROJECT_TITLE":"Antimalarial pantothenamide metabolites target acetyl-CoA biosynthesis in Plasmodium falciparum","PROJECT_SUMMARY":"Malaria eradication is critically dependent on new therapeutics that target resistant Plasmodium parasites and block transmission of the disease. Here, we report the discovery of potent pantothenamide bioisosteres that are active against blood-stage Plasmodium falciparum parasites and that block transmission of sexual stages to the mosquito vector. These compounds were resistant to degradation by serum pantetheinases, showed favorable pharmacokinetic properties and cleared parasites in a humanized mouse infection model of P. falciparum. Metabolomics revealed that CoA biosynthetic enzymes converted pantothenamides into CoA-analogs that interfered with parasite acetyl-CoA anabolism. In vitro generated resistant parasites showed mutations in acetyl-CoA synthetase and acyl-CoA synthetase 11. Introduction and reversion of these mutations in P. falciparum by CRISPR/Cas9 gene editing confirmed the key roles of these enzymes in the sensitivity of the malaria parasite to pantothenamides. These pantothenamide compounds with a unique mode of action may have potential as drugs against malaria parasites.","INSTITUTE":"Penn State","LAST_NAME":"Llinas","FIRST_NAME":"Manuel","ADDRESS":"W126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA","EMAIL":"mul27@psu.edu","PHONE":"(814) 867-3527"},

"STUDY":{"STUDY_TITLE":"NMR assignment of synthetic pantothenamides (part-II)","STUDY_SUMMARY":"1H and 13C NMR of synthesized pantothenamides used for in vitro metabolomics studies.","INSTITUTE":"Penn State","LAST_NAME":"Llinas","FIRST_NAME":"Manuel","ADDRESS":"W126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA","EMAIL":"mul27@psu.edu","PHONE":"(814) 867-3527"},

"SUBJECT":{"SUBJECT_TYPE":"Other","SUBJECT_SPECIES":"Synthetic"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"006_1H",
"Factors":{"Spectra":"1H NMR"},
"Additional sample data":{"Type":"CXP18.6-006"}
},
{
"Subject ID":"-",
"Sample ID":"006_13C",
"Factors":{"Spectra":"13C NMR"},
"Additional sample data":{"Type":"CXP18.6-006"}
},
{
"Subject ID":"-",
"Sample ID":"017_1H",
"Factors":{"Spectra":"1H NMR"},
"Additional sample data":{"Type":"CXP18.6-017"}
},
{
"Subject ID":"-",
"Sample ID":"017_13C",
"Factors":{"Spectra":"13C NMR"},
"Additional sample data":{"Type":"CXP18.6-017"}
},
{
"Subject ID":"-",
"Sample ID":"026_1H",
"Factors":{"Spectra":"1H NMR"},
"Additional sample data":{"Type":"CXP18.6-026"}
},
{
"Subject ID":"-",
"Sample ID":"026_13C",
"Factors":{"Spectra":"13C NMR"},
"Additional sample data":{"Type":"CXP18.6-026"}
},
{
"Subject ID":"-",
"Sample ID":"052_1H",
"Factors":{"Spectra":"1H NMR"},
"Additional sample data":{"Type":"CXP18.6-052"}
},
{
"Subject ID":"-",
"Sample ID":"052_13C",
"Factors":{"Spectra":"13C NMR"},
"Additional sample data":{"Type":"CXP18.6-052"}
},
{
"Subject ID":"-",
"Sample ID":"052_HSQC",
"Factors":{"Spectra":"HSQC NMR"},
"Additional sample data":{"Type":"CXP18.6-052"}
},
{
"Subject ID":"-",
"Sample ID":"258_1H",
"Factors":{"Spectra":"1H NMR"},
"Additional sample data":{"Type":"MMV689258"}
},
{
"Subject ID":"-",
"Sample ID":"258_13C",
"Factors":{"Spectra":"13C NMR"},
"Additional sample data":{"Type":"MMV689258"}
},
{
"Subject ID":"-",
"Sample ID":"968_1H",
"Factors":{"Spectra":"1H NMR"},
"Additional sample data":{"Type":"MMV884968"}
},
{
"Subject ID":"-",
"Sample ID":"968_13C",
"Factors":{"Spectra":"13C NMR"},
"Additional sample data":{"Type":"MMV884968"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Synthesized compounds were freeze dried and resuspended in MeOD between 10-20mM. Samples were then placed into NMR sample tubes for analysis.","SAMPLE_TYPE":"Synthetic chemistry"},

"TREATMENT":{"TREATMENT_SUMMARY":"No treatment, these synthetic compounds tested for structure accuracy and purity."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Several of the original synthesized compounds were in DMSO. This was removed, to the best of our ability, using a freeze dryer before dissolving in MeOD."},

"ANALYSIS":{"ANALYSIS_TYPE":"NMR"},

"NM":{"INSTRUMENT_NAME":"Bruker AVIII-HD-500","INSTRUMENT_TYPE":"FT-NMR","NMR_EXPERIMENT_TYPE":"Other","SPECTROMETER_FREQUENCY":"500 MHz"}

}