title: PEG based resins for protease drug discovery synthesis, screening and analysis of combinatorial on-bead libraries.
abstract: This review will cover the entire hit identification process performed with biocompatible, aqueous solvated, poly[ethylene glycol] (PEG) based resins - from synthesis, through screening, to analysis. The different types of resins (including their preparation) will be discussed and compared individually. Examples of one-bead-one-compound substrate libraries will be presented, as will one-bead-two-compounds libraries used for the discovery of enzyme inhibitors. The review includes a section covering organic and bio-organic reactions performed on all-PEG resins and discusses on-bead screening of the libraries with biomolecules. Finally, analysis of compounds on single beads, either via investigation by on-bead NMR or by ladder-coding of the combinatorial compound is covered. In general, the review will focus on chemistry, libraries, synthesis, screening, and analysis, using all-PEG based resins.
authors.affiliation: Department of Medicinal Chemistry, Combio A/S, Gamle Carlsberg Vej 10, DK-2500 Valby, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Groth
authors.forename: Manat
authors.initials: M
authors.lastname: Renil
authors.forename: Ernst
authors.initials: E
authors.lastname: Meinjohanns
mesh_terms: D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D008863:Microspheres; D011092:Polyethylene Glycols; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D012117:Resins, Synthetic / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D012117:Resins, Synthetic; D011092:Polyethylene Glycols