title: Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides.
abstract: The enoyl acyl-carrier protein reductase (ENR) enzyme is harbored within the apicoplast of apicomplexan parasites providing a significant challenge for drug delivery, which may be overcome through the addition of transductive peptides, which facilitates crossing the apicoplast membranes. The binding site of triclosan, a potent ENR inhibitor, is occluded from the solvent making the attachment of these linkers challenging. Herein, we have produced 3 new triclosan analogs with bulky A- and B-ring motifs, which protrude into the solvent allowing for the future attachment of molecular transporters for delivery.
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds, UK. s.p.muench@leeds.ac.uk
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Muench
authors.forename: Jozef
authors.initials: J
authors.lastname: Stec
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Afanador
authors.forename: Martin J
authors.initials: MJ
authors.lastname: McPhillie
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hickman
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Lee
authors.forename: Susan E
authors.initials: SE
authors.lastname: Leed
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Auschwitz
authors.forename: Sean T
authors.initials: ST
authors.lastname: Prigge
authors.forename: David W
authors.initials: DW
authors.lastname: Rice
authors.forename: Rima
authors.initials: R
authors.lastname: McLeod
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000378:metabolism; D014122:Toxoplasma / Q000378:metabolism; D014260:Triclosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D014260:Triclosan; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)