Design, preparation, and selection of DNA-encoded dynamic libraries.

نویسندگان

  • Gang Li
  • Wenlu Zheng
  • Zitian Chen
  • Yu Zhou
  • Yu Liu
  • Junrui Yang
  • Yanyi Huang
  • Xiaoyu Li
چکیده

We report a method for the preparation and selection of DNA-encoded dynamic libraries (DEDLs). The library is composed of two sets of DNA-linked small molecules that are under dynamic exchange through DNA hybridization. Addition of the protein target shifted the equilibrium, favouring the assembly of high affinity bivalent binders. Notably, we introduced a novel locking mechanism to stop the dynamic exchange and "freeze" the equilibrium, thereby enabling downstream hit isolation and decoding by PCR amplification and DNA sequencing. Our DEDL approach has circumvented the limitation of library size and realized the analysis and selection of large dynamic libraries. In addition, this method also eliminates the requirement for modified and immobilized target proteins.

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منابع مشابه

Design, preparation, and selection of DNA-encoded dynamic libraries† †Electronic supplementary information (ESI) available: Materials and general methods, experimental details, library selection and sequencing methods and fold enrichment calculations. See DOI: 10.1039/c5sc02467f Click here for additional data file.

Key Laboratory of Bioorganic Chemistry and Education, Beijing National Laboratory of Chemistry and Molecular Engineering, Pe E-mail: [email protected] Key Laboratory of Chemical Genomics, Scho Peking University Shenzhen Graduate Schoo Biodynamic Optical Imaging Centre (BIOP University, Beijing, China 100871 † Electronic supplementary information methods, experimental details, library se fold ...

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عنوان ژورنال:
  • Chemical science

دوره 6 12  شماره 

صفحات  -

تاریخ انتشار 2015