title: Revealing the Macromolecular Targets of Fragment-Like Natural Products.
abstract: Fragment-like natural products were identified as ligand-efficient chemical matter for hit-to-lead development and chemical-probe discovery. Relying on a computational method using a topological pharmacophore descriptor and a drug database, several macromolecular targets from distinct protein families were expeditiously retrieved for structurally unrelated chemotypes. The selected fragments feature structural dissimilarity to the reference compounds and suitable target affinity, and they offer opportunities for chemical optimization. Experimental confirmation of hitherto unknown macromolecular targets for the selected molecules corroborate the usefulness of the computational approach and suggests broad applicability to chemical biology and molecular medicine.
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Daniel
authors.initials: D
authors.lastname: Reker
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Jens
authors.initials: J
authors.lastname: Kunze
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland). gisbert.schneider@pharma.ethz.ch.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry*
chemical_list: D001688:Biological Products; D046911:Macromolecular Substances
keywords: chemical biology; computer-assisted drug design; drug discovery; medicinal chemistry; target identification