DNA编码化合物库在小分子药物发现中的应用.pdf

This article was published as part of the Advances in DNA-based nanotechnology themed issue Guest editors Eugen Stulz, Guido Clever, Mitsuhiko Shionoya and Chengde Mao Please take a look at the issue 12 2011 table of contents to access other reviews in this themed issue Chem Soc Rev Dynamic Article Links Cite this: Chem. Soc. Rev., 2011, 40, 5707–5717 /csr TUTORIAL REVIEW Small-molecule discovery from DNA-encoded chemical librariesw Ralph E. Kleiner,z Christoph E. Dumelinz and David R. Liu* Received 23rd March 2011 DOI: 10.1039/c1cs15076f Researchers seeking to improve the efficiency and cost effectiveness of the bioactive small-molecule discovery process have recently embraced selection-based approaches, which in principle offer much higher throughput and simpler infrastructure requirements compared with traditional small-molecule screening methods. Since selection methods benefit greatly from an information-encoding molecule that can be readily amplified and decoded, several academic and industrial groups have turned to DNA as the basis for library encoding and, in some cases, library synthesis. The resulting DNA-encoded synthetic small-molecule libraries, integrated with the high sensitivity of PCR and the recent development of ultra high-throughput DNA sequencing technology, can be evaluated very rapidly for binding or bond formation with a target of interest while consuming minimal quantities of material and requiring only modest investments of time and equipment. In this tutorial review we describe the development of two classes of approaches for encoding chemical structures and reactivity with DNA: DNA-recorded library synthesis, in which encoding and library synthesis take