RT Journal Article
SR Electronic
T1 Diverse chemical functionalization of nucleobases within long RNAs using sulfinate salts
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.19.465008
DO 10.1101/2021.10.19.465008
A1 Gomez, Anastassia
A1 Bassi, Tiziano
A1 Grayson, Leah
A1 Vantourout, Julien
A1 Toor, Navtej
YR 2021
UL http://biorxiv.org/content/early/2021/10/19/2021.10.19.465008.abstract
AB We have devised a single pot, low-cost method to modify RNA with sulfinate salts that can directly add almost any desired functional group to nucleobases under mild aqueous conditions. This chemistry modifies the Hoogsteen edge of RNA and DNA nucleobases. It can be applied to RNA or DNA of any size, as well as to individual nucleotides. Existing methods of RNA modification have relatively limited applicability due to constraints on the size of the RNA and the lack of diversity of possible modifications. We have been able to add azide groups for click reactions directly onto the nucleobases of RNA utilizing sulfinate salts. C-H bonds on the nucleobase aromatic rings serve as the sites of attachment, with C-H being replaced with C-R, where R is the azide-containing linker. With the addition of azide functional groups, the modified RNA can easily be reacted with any alkyne-labeled compound of interest, including fluorescent dyes as shown in this work. This methodology enables the exploration of diverse chemical groups on RNA that can potentially confer protection from nucleases, allow for efficient delivery of nucleic acids into cells, or act as new tools for the investigation of nucleic acid structure and function.Competing Interest StatementAH and NT have obtained a patent on the sulfinate modification of nucleic acids.