Disulfide conjugation of peptides to oligonucleotides and their analogs.

Current Protocols in Nucleic Acid Chemistry
John J TurnerMichael J Gait

Abstract

Peptide conjugation of oligonucleotides and their analogs is being studied widely towards improving the delivery of oligonucleotides into cells. Amongst the many possible routes of conjugation, the disulfide linkage has proved to be the most popular. This reversible linkage may have advantages for cell delivery, since it is likely to be cleaved within cells, thus releasing the oligonucleotide cargo. It is straightforward to introduce thiol functionalities into both oligonucleotide and peptide components suitable for disulfide conjugation. However, severe difficulties have been encountered in carrying out conjugations between highly cationic peptides and negatively charged oligonucleotides because of aggregation and precipitation. Presented here are reliable protocols for disulfide conjugation that have been verified for both cationic and hydrophobic peptides as well as oligonucleotides containing deoxyribonucleosides, ribonucleosides, 2'-O-methylribonucleosides, locked nucleic acid (LNA) units, as well as phosphorothioate backbones. Also presented are reliable protocols for disulfide conjugation of peptide nucleic acids (PNAs) with peptides.

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Citations

May 5, 2011·Journal of the American Chemical Society·Keith T GagnonDavid R Corey
Jan 25, 2013·Molecular Therapy. Nucleic Acids·Peter JärverMichael J Gait
Oct 19, 2017·International Journal of Molecular Medicine·Maciej GagatAlina Grzanka
Sep 19, 2015·Current Protocols in Nucleic Acid Chemistry·Shigeori Takenaka

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