Scientific Article
previous document  unige:24693  next document
add to browser collection
Title

DNA-templated combinatorial assembly of small molecule fragments amenable to selection/amplification cycles

Authors
Ciobanu, Mihai
Alvarez, Susana
Barluenga, Sofia
Published in Chemical Science. 2011, vol. 2, no. 4, p. 625-632
Abstract The discovery of small molecule probes which selectively modulate biological pathways is a cornerstone in the development of new therapeutics. Progress in our ability to access libraries of biologically relevant small molecules in conjunction with streamlined screening technologies have also enabled a more systematic approach to chemical biology. Nevertheless, the current state of the art still requires a large infrastructure and only a small fraction of the proteome has been addressed thus far. The emergence of technologies based on nucleic acid encoding of small molecules presents a new screening paradigm. We describe a method based on DNA-templated combinatorial display of PNA-encoded drug fragments affording 62500 combinations which can be amplified following a selection. This concept was demonstrated with a screen against a representative target, carbonic anhydrase, by iterative cycles of affinity selection, amplification of DNA template and “translation” back into selected library members. The results show a clear convergence towards combinations which, upon resynthesis as covalent adducts, proved to bind cooperatively to carbonic anhydrase.
Identifiers
Full text
Article (Published version) (1 MB) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://xlink.rsc.org/?DOI=c0sc00574f
Citation
(ISO format)
DAGUER, Jean Pierre et al. DNA-templated combinatorial assembly of small molecule fragments amenable to selection/amplification cycles. In: Chemical Science, 2011, vol. 2, n° 4, p. 625-632. https://archive-ouverte.unige.ch/unige:24693

192 hits

5 downloads

Update

Deposited on : 2012-12-18

Export document
Format :
Citation style :