title: Design of compound libraries based on natural product scaffolds and protein structure similarity clustering (PSSC).
abstract: Recent advances in structural biology, bioinformatics and combinatorial chemistry have significantly impacted the discovery of small molecules that modulate protein functions. Natural products which have evolved to bind to proteins may serve as biologically validated starting points for the design of focused libraries that might provide protein ligands with enhanced quality and probability. The combined application of natural product derived scaffolds with a new approach that clusters proteins according to structural similarity of their ligand sensing cores provides a new principle for the design and synthesis of such libraries. This article discusses recent advances in the synthesis of natural product inspired compound collections and the application of protein structure similarity clustering for the development of such libraries.
authors.affiliation: Department of Chemical Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Rengarajan
authors.initials: R
authors.lastname: Balamurugan
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Dekker
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000737:chemistry; D000110:Acetylcholinesterase / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry; D020687:cdc25 Phosphatases / Q000737:chemistry
chemical_list: D001688:Biological Products; D004791:Enzyme Inhibitors; D008024:Ligands; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000110:Acetylcholinesterase; D020687:cdc25 Phosphatases