DNA-encoded chemistry: enabling the deeper sampling of chemical space

被引：456

作者：

Goodnow, Robert A., Jr. ^{[1
,2
]}

Dumelin, Christoph E. ^{[3
]}

Keefe, Anthony D. ^{[4
]}

机构：

[1] AstraZeneca, Discovery Sci Innovat Med & Early Dev Biotech Uni, Waltham, MA 02451 USA

[2] Pharmaron Inc, Boston, MA 02451 USA

[3] Novartis Pharma AG, Novartis Inst Biomed Res, CH-4033 Basel, Switzerland

[4] X Chem, Waltham, MA 02453 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2017年 / 16卷 / 02期

关键词：

IN-VITRO SELECTION; LIBRARY TECHNOLOGY ELT; MYCOBACTERIUM-TUBERCULOSIS INHA; IONIZATION MASS-SPECTROMETRY; SMALL-MOLECULE LIBRARIES; LIGAND-TARGET PAIRS; TEMPLATED SYNTHESIS; COMBINATORIAL CHEMISTRY; ORGANIC-SYNTHESIS; KINASE INHIBITORS;

D O I：

10.1038/nrd.2016.213

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

DNA-encoded chemical library technologies are increasingly being adopted in drug discovery for hit and lead generation. DNA-encoded chemistry enables the exploration of chemical spaces four to five orders of magnitude more deeply than is achievable by traditional high-throughput screening methods. Operation of this technology requires developing a range of capabilities including aqueous synthetic chemistry, building block acquisition, oligonucteotide conjugation, large-scale molecular biological transformations, selection methodologies, PCR, sequencing, sequence data analysis and the analysis of large chemistry spaces. This Review provides an overview of the development and applications of DNA-encoded chemistry, highlighting the challenges and future directions for the use of this technology.

引用

页码：131 / 147

页数：17

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