title: Structure guided development of potent reversibly binding penicillin binding protein inhibitors.
abstract: Following from the evaluation of different types of electrophiles, combined modeling and crystallographic analyses are used to generate potent boronic acid based inhibitors of a penicillin binding protein. The results suggest that a structurally informed approach to penicillin binding protein inhibition will be useful for the development of both improved reversibly binding inhibitors, including boronic acids, and acylating inhibitors, such as β-lactams.
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford , 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Esther C Y
authors.initials: EC
authors.lastname: Woon
authors.affiliation: Centre de Recherches du Cyclotron, B30, Universite de Liège , Sart-Tilman, B-4000 Liège, Belgium.
authors.forename: Astrid
authors.initials: A
authors.lastname: Zervosen
authors.affiliation: Centre d'Ingénierie des Protéines, Université de Liège , Institut de Physique B5, B-4000 Liège, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Sauvage
authors.affiliation: School of Chemistry, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Simmons
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Matej
authors.initials: M
authors.lastname: Zivec
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford , 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Inglis
authors.affiliation: School of Chemistry, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Colin W G
authors.initials: CW
authors.lastname: Fishwick
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.affiliation: Centre d'Ingénierie des Protéines, Université de Liège , Institut de Physique B5, B-4000 Liège, Belgium.
authors.forename: Paulette
authors.initials: P
authors.lastname: Charlier
authors.affiliation: Centre de Recherches du Cyclotron, B30, Universite de Liège , Sart-Tilman, B-4000 Liège, Belgium.
authors.forename: André
authors.initials: A
authors.lastname: Luxen
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford , 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
keywords: Penicillin binding proteins; antibiotic-resistance; antibiotics; boronic acids; transpeptidase-inhibition; β-lactams