title: Thiourea-based spacers in potent divalent inhibitors of Pseudomonas aeruginosa virulence lectin LecA.
abstract: A new divalent highly potent inhibitor of the Pseudomonas aeruginosa lectin and virulence factor LecA was prepared. It contains two thiourea linkages which were found to be in the Z,Z isomeric form. This brings the spacer into an elongated conformation required to bridge the two binding sites, which results in the chelating binding mode responsible for the high potency.
authors.affiliation: Department of Medicinal Chemistry & Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB, Utrecht, The Netherlands. R.J.Pieters@uu.nl.
authors.forename: Aliaksei V
authors.initials: AV
authors.lastname: Pukin
authors.forename: Arwin J
authors.initials: AJ
authors.lastname: Brouwer
authors.forename: Leonie
authors.initials: L
authors.lastname: Koomen
authors.forename: H C
authors.initials: HC
authors.lastname: Quarles van Ufford
authors.forename: Johan
authors.initials: J
authors.lastname: Kemmink
authors.forename: Nico J
authors.initials: NJ
authors.lastname: de Mol
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Pieters
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D037102:Lectins / Q000037:antagonists & inhibitors / Q000378:metabolism; D062105:Molecular Docking Simulation; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; C102929:LecA protein, bacteria; D037102:Lectins; D037521:Virulence Factors; D013890:Thiourea