Design, synthesis and selection of DNA-encoded small-molecule libraries.
Nat Chem Biol
; 5(9): 647-54, 2009 Sep.
Article
in En
| MEDLINE
| ID: mdl-19648931
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
Drug Design
/
Protein Kinase Inhibitors
/
Small Molecule Libraries
Limits:
Animals
Language:
En
Journal:
Nat Chem Biol
Journal subject:
BIOLOGIA
/
QUIMICA
Year:
2009
Type:
Article
Affiliation country:
United States