title: Geminal dihalogen isosteric replacement in hydrated AI-2 affords potent quorum sensing modulators.
abstract: Hydrated carbonyl groups in AI-2, a quorum sensing autoinducer, make key hydrogen bonding interactions in the binding site of LsrR (a transcriptional regulator). This can be recapitulated with geminal dibromides, via halogen bonding. Geminal dihalogens represent interesting isosteric replacements for hydrated carbonyls in ligands and are currently under-utilized in ligand design.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland College Park, 20742, USA. hsintim@umd.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Yue
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Terell
authors.forename: Michal
authors.initials: M
authors.lastname: Ad
authors.forename: Clement
authors.initials: C
authors.lastname: Opoku-Temeng
authors.forename: William E
authors.initials: WE
authors.lastname: Bentley
authors.forename: Herman O
authors.initials: HO
authors.lastname: Sintim
mesh_terms: D001665:Binding Sites; D029968:Escherichia coli Proteins / Q000378:metabolism; D006714:Homoserine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D029968:Escherichia coli Proteins; D007783:Lactones; D008024:Ligands; C504601:LsrR protein, E coli; C091088:N-octanoylhomoserine lactone; D012097:Repressor Proteins; D014867:Water; D006714:Homoserine