TY - JOUR
T1 - Mercury-Free Automated Synthesis of Guanidinium Backbone Oligonucleotides
AU - Skakuj, Kacper
AU - Bujold, Katherine E.
AU - Mirkin, Chad A.
N1 - Funding Information:
We would like to acknowledge support from the Vannevar Bush Faculty Fellowship program sponsored by the Basic Research Office of the Assistant Secretary of Defense for Research and Engineering and funded by the Office of Naval Research through grant N00014-15-1-0043; the Prostate Cancer Foundation and the Movember Foundation under award 17CHAL08; and the National Cancer Institute of the National Institutes of Health under award U54CA199091. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work made use of the IMSERC at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205), the State of Illinois, and the International Institute for Nanotechnology (IIN). K.E.B. is supported by a Banting Fellowship from the Government of Canada. We would like to thank Professor Karl A. Scheidt for helpful and illuminating discussions.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/12/26
Y1 - 2019/12/26
N2 - A new method for synthesizing deoxynucleic guanidine (DNG) oligonucleotides that uses iodine as a mild and inexpensive coupling reagent is reported. This method eliminates the need for the toxic mercury salts and pungent thiophenol historically used in methods aimed at preparing DNG oligonucleotides. This coupling strategy was readily translated to a standard MerMade 12 oligonucleotide synthesizer with coupling yields of 95% and has enabled the synthesis of a 20-mer DNG oligonucleotide, the longest DNG strand to date, in addition to mixed DNA-DNG sequences with 3-9 DNG inserts. Importantly, DNG oligonucleotides exhibit robust unaided cellular uptake as compared to unmodified oligonucleotides without apparent cellular toxicity. Taken together, these findings should greatly increase the accessibility of cationic backbone modifications and assist in the development of oligonucleotide-based drugs.
AB - A new method for synthesizing deoxynucleic guanidine (DNG) oligonucleotides that uses iodine as a mild and inexpensive coupling reagent is reported. This method eliminates the need for the toxic mercury salts and pungent thiophenol historically used in methods aimed at preparing DNG oligonucleotides. This coupling strategy was readily translated to a standard MerMade 12 oligonucleotide synthesizer with coupling yields of 95% and has enabled the synthesis of a 20-mer DNG oligonucleotide, the longest DNG strand to date, in addition to mixed DNA-DNG sequences with 3-9 DNG inserts. Importantly, DNG oligonucleotides exhibit robust unaided cellular uptake as compared to unmodified oligonucleotides without apparent cellular toxicity. Taken together, these findings should greatly increase the accessibility of cationic backbone modifications and assist in the development of oligonucleotide-based drugs.
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U2 - 10.1021/jacs.9b09937
DO - 10.1021/jacs.9b09937
M3 - Article
C2 - 31840508
AN - SCOPUS:85077115510
SN - 0002-7863
VL - 141
SP - 20171
EP - 20176
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 51
ER -