4.7 Article

Modular Strategy To Expand the Chemical Diversity of DNA and Sequence-Controlled Polymers

Journal

JOURNAL OF ORGANIC CHEMISTRY
Volume 83, Issue 17, Pages 9774-9786

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.joc.8b01184

Keywords

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Funding

  1. NSERC
  2. CIHR
  3. FRQNT
  4. Canada Research Chairs program
  5. Qatar National Research Fund (QNRF) [NPRP 5-1505-1-250]

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Sequence-defined polymers with customizable sequences, monodispersity, substantial length, and large chemical diversity are of great interest to mimic the efficiency and selectivity of biopolymers. We report an efficient, facile, and scalable synthetic route to introduce many chemical functionalities, such as amino acids and sugars in nucleic acids and sequence-controlled oligophosphodiesters. Through achiral tertiary amine molecules that are perfectly compatible with automated DNA synthesis, readily available amines or azides can be turned into phosphoramidites in two steps only. Individual attachment yields on nucleic acids and artificial oligophosphodiesters using automated solid-phase synthesis (SPS) were >90% in almost all cases. Using this method, multiple water-soluble sequence-defined oligomers bearing a range of functional groups in precise sequences could be synthesized and purified in high yields. The method described herein significantly expands the library of available functionalities for nucleic acids and sequence-controlled polymers.

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