2. Academic Validation
  3. Design, synthesis and selection of DNA-encoded small-molecule libraries

Design, synthesis and selection of DNA-encoded small-molecule libraries

  • Nat Chem Biol. 2009 Sep;5(9):647-54. doi: 10.1038/nchembio.211.
Matthew A Clark 1,  Raksha A Acharya,  Christopher C Arico-Muendel,  Svetlana L Belyanskaya,  Dennis R Benjamin,  Neil R Carlson,  Paolo A Centrella,  Cynthia H Chiu,  Steffen P Creaser,  John W Cuozzo,  Christopher P Davie,  Yun Ding,  G Joseph Franklin,  Kurt D Franzen,  Malcolm L Gefter,  Steven P Hale,  Nils J V Hansen,  David I Israel,  Jinwei Jiang,  Malcolm J Kavarana,  Michael S Kelley,  Christopher S Kollmann,  Fan Li,  Kenneth Lind,  Sibongile Mataruse,  Patricia F Medeiros,  Jeffrey A Messer,  Paul Myers,  Heather O'Keefe,  Matthew C Oliff,  Cecil E Rise,  Alexander L Satz,  Steven R Skinner,  Jennifer L Svendsen,  Lujia Tang,  Kurt van Vloten,  Richard W Wagner,  Gang Yao,  Baoguang Zhao,  Barry A Morgan
Affiliations

Affiliation

  • 1 Praecis Pharmaceuticals, Waltham, Massachusetts, USA
PMID: 19648931 DOI: 10.1038/nchembio.211
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.

Figures
Products