Advertisement

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.

ENJOY UNLIMITED ACCES TO C&EN

Synthesis

DNA Bar Codes For Libraries

Methods have screened 800 million compounds for kinase inhibitors

by Laura Cassiday
August 10, 2009 | A version of this story appeared in Volume 87, Issue 32

[+]Enlarge
Credit: Adapted from Nat. Chem. Biol.
The sequence of a DNA tag identified attached small molecules in an 800 million-member chemical library.
Credit: Adapted from Nat. Chem. Biol.
The sequence of a DNA tag identified attached small molecules in an 800 million-member chemical library.

A research team led by Barry A. Morgan of GlaxoSmithKline has synthesized and screened a DNA-encoded library of 800 million small molecules to identify enzyme inhibitors (Nat. Chem. Biol., DOI: 10.1038/nchembio.211). Not only does the new method offer an unusually large library size for small-molecule screening, but it's also fast and relatively inexpensive, requiring less than 1 mg of target protein. Each small molecule, which consists of four chemically diverse building blocks, is attached to a unique DNA bar code that, upon sequencing, reveals the molecule's chemical composition. Starting with a short covalently linked double-stranded DNA "headpiece," the researchers constructed the library with four rounds of chemical synthesis, ligating a specific sequence of duplex DNA to the headpiece for each chemical building block added to the other end. Three rounds of affinity selection with the 800 million-member library and high-throughput sequencing of DNA tags revealed potential p38 MAP kinase inhibitors. "We believe that this technique could revolutionize the discovery of small-molecule modulators of biological targets," the researchers write.

Article:

This article has been sent to the following recipient:

0 /1 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.