title: Halogen-enriched fragment libraries as chemical probes for harnessing halogen bonding in fragment-based lead discovery.
abstract: Halogen bonding has recently experienced a renaissance, gaining increased recognition as a useful molecular interaction in the life sciences. Halogen bonds are favorable, fairly directional interactions between an electropositive region on the halogen (the σ-hole) and a number of different nucleophilic interaction partners. Some aspects of halogen bonding are not yet understood well enough to take full advantage of its potential in drug discovery. We describe and present the concept of halogen-enriched fragment libraries. These libraries consist of unique chemical probes, facilitating the identification of favorable halogen bonds by sharing the advantages of classical fragment-based screening. Besides providing insights into the nature and applicability of halogen bonding, halogen-enriched fragment libraries provide smart starting points for hit-to-lead evolution.
authors.affiliation: Department of Pharmaceutical & Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard-Karls-University Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany.
authors.forename: Markus O
authors.initials: MO
authors.lastname: Zimmermann
authors.forename: Andreas
authors.initials: A
authors.lastname: Lange
authors.forename: Rainer
authors.initials: R
authors.lastname: Wilcken
authors.forename: Markus B
authors.initials: MB
authors.lastname: Cieslik
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Exner
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Joerger
authors.forename: Pierre
authors.initials: P
authors.lastname: Koch
authors.forename: Frank M
authors.initials: FM
authors.lastname: Boeckler
mesh_terms: D000818:Animals; D001665:Binding Sites; D030562:Databases, Protein; D015195:Drug Design; D006219:Halogens / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D006219:Halogens; D011506:Proteins; D054852:Small Molecule Libraries