2024
A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria
Chahine Z, Abel S, Hollin T, Barnes G, Chung J, Daub M, Renard I, Choi J, Vydyam P, Pal A, Alba-Argomaniz M, Banks C, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C, Bei A, Florens L, Ben Mamoun C, Vanderwal C, Le Roch K. A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria. Science 2024, 385: eadm7966. PMID: 39325875, DOI: 10.1126/science.adm7966.Peer-Reviewed Original ResearchConceptsP. falciparum malariaHumanized mouse modelPlasmodium falciparum</i> strainsIn vivo studiesParasite apicoplastDrug sensitivityTherapeutic profileVesicular traffickingGenomic analysisLipid biogenesisSecretory machineryAsexual replicationGenetic analysisReduced susceptibilityCellular traffickingApicoplast functionStrong efficacyMED6Sexual differentiationHemolytic activityDrug pipelineApicoplastKalihinolTraffickingMalaria
2019
Benzimidazolinone-Free Peptide o‑Aminoanilides for Chemical Protein Synthesis
Mannuthodikayil J, Singh S, Biswas A, Kar A, Tabassum W, Vydyam P, Bhattacharyya M, Mandal K. Benzimidazolinone-Free Peptide o‑Aminoanilides for Chemical Protein Synthesis. Organic Letters 2019, 21: 9040-9044. PMID: 31663760, DOI: 10.1021/acs.orglett.9b03440.Peer-Reviewed Original ResearchConceptsPeptide synthesisSolid-phase peptide synthesisChemical protein synthesisPhase peptide synthesisTotal chemical synthesisSerious side reactionsPeptide thioestersChemical synthesisEfficient synthesisSide reactionsDiaminobenzoic acidO-aminoanilidesSynthesisThioestersAminesBocFormationCarbamateHereinReactionOptional attachmentSolubility tagAcidPeptidesC-terminusA small-molecule inhibitor of the DNA recombinase Rad51 from Plasmodium falciparum synergizes with the antimalarial drugs artemisinin and chloroquine
Vydyam P, Dutta D, Sutram N, Bhattacharyya S, Bhattacharyya M. A small-molecule inhibitor of the DNA recombinase Rad51 from Plasmodium falciparum synergizes with the antimalarial drugs artemisinin and chloroquine. Journal Of Biological Chemistry 2019, 294: 8171-8183. PMID: 30936202, PMCID: PMC6527153, DOI: 10.1074/jbc.ra118.005009.Peer-Reviewed Original ResearchConceptsMultidrug-resistant parasitesAnti-parasitic activitySmall molecule inhibitorsMalaria drugsAntimalarial drugsChloroquinePotential drug targetsAntigenic diversityAntimalarial activityCell linesParasitic DNADNA double-strand breaksSpecific inhibitorDrug targetsDrugsInhibitorsParasitesPfRad51DNA-damaging agentsHigh affinityScreening approachFindingsHomologous recombinationMammalian cell linesActivity