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

Abstract

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.

Uptake and Fate of Fluorescently Labeled DNA Nanostructures in Cellular Environments: A Cautionary Tale

“…46 We used click chemistry and one of our previously developed phosphoramidites to label the cube clip with a sulfonated Cy5 at its 5′-end or in an internal position (Figure 7B and Figures S91 and S92). 47 The sulfonated clip and cube gave little fluorescent signal inside cells compared to the non-sulfonated Cy5 (Figure 7C and Figure S93). This means that the intracellular fluorescence is dye-dependent and that low fluorescent signal, sometimes observed from other dyes can not be correlated with uptake of the structure.…”

Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)

“… 18,38 In comparison to other SNAs, our sequence-controlled polymeric SNAs are made from biocompatible, biodegradable materials, can encapsulate small molecule drugs and allow for near infinite variation in polymer chemistry and sequence in an automated fashion. 39 This gives them distinct advantages in biocompatibility and ease of synthesis, as well as control of size, shape, and function. 28 …”

DNA-Programmed Chemical Synthesis of Polymers and Inorganic Nanomaterials

“…However, it has been possible to achieve controlled polymer molecules by taking advantage of DNA sequences to guide the polymerization process. The technology of DNA-encoded polymer synthesis is devoted to more accurate design and preparation of polymer materials, and more precise control of their structure and function [24,25].…”