title: Design, synthesis and selection of DNA-encoded small-molecule libraries.
abstract: Biochemical combinatorial techniques such as phage display, RNA display and oligonucleotide aptamers have proven to be reliable methods for generation of ligands to protein targets. Adapting these techniques to small synthetic molecules has been a long-sought goal. We report the synthesis and interrogation of an 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide. The library was assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection. We describe methods for the selection and deconvolution of the chemical display library, and the discovery of inhibitors for two enzymes: Aurora A kinase and p38 MAP kinase.
authors: Praecis Pharmaceuticals, Waltham, Massachusetts, USA
authors: Matthew A
authors: MA
authors: Clark
authors: Raksha A
authors: RA
authors: Acharya
authors: Christopher C
authors: CC
authors: Arico-Muendel
authors: Svetlana L
authors: SL
authors: Belyanskaya
authors: Dennis R
authors: DR
authors: Benjamin
authors: Neil R
authors: NR
authors: Carlson
authors: Paolo A
authors: PA
authors: Centrella
authors: Cynthia H
authors: CH
authors: Chiu
authors: Steffen P
authors: SP
authors: Creaser
authors: John W
authors: JW
authors: Cuozzo
authors: Christopher P
authors: CP
authors: Davie
authors: Yun
authors: Y
authors: Ding
authors: G Joseph
authors: GJ
authors: Franklin
authors: Kurt D
authors: KD
authors: Franzen
authors: Malcolm L
authors: ML
authors: Gefter
authors: Steven P
authors: SP
authors: Hale
authors: Nils J V
authors: NJ
authors: Hansen
authors: David I
authors: DI
authors: Israel
authors: Jinwei
authors: J
authors: Jiang
authors: Malcolm J
authors: MJ
authors: Kavarana
authors: Michael S
authors: MS
authors: Kelley
authors: Christopher S
authors: CS
authors: Kollmann
authors: Fan
authors: F
authors: Li
authors: Kenneth
authors: K
authors: Lind
authors: Sibongile
authors: S
authors: Mataruse
authors: Patricia F
authors: PF
authors: Medeiros
authors: Jeffrey A
authors: JA
authors: Messer
authors: Paul
authors: P
authors: Myers
authors: Heather
authors: H
authors: O'Keefe
authors: Matthew C
authors: MC
authors: Oliff
authors: Cecil E
authors: CE
authors: Rise
authors: Alexander L
authors: AL
authors: Satz
authors: Steven R
authors: SR
authors: Skinner
authors: Jennifer L
authors: JL
authors: Svendsen
authors: Lujia
authors: L
authors: Tang
authors: Kurt
authors: K
authors: van Vloten
authors: Richard W
authors: RW
authors: Wagner
authors: Gang
authors: G
authors: Yao
authors: Baoguang
authors: B
authors: Zhao
authors: Barry A
authors: BA
authors: Morgan
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D020650:Combinatorial Chemistry Techniques; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D015195:Drug Design; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D004247:DNA; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases