Open AccessOligonucleotides Containing 1-Aminomethyl or 1-Mercaptomethyl-2-deoxy-d -ribofuranoses: Synthesis, Purification, Characterization, and Conjugation with Fluorophores and Lipids
Author(s) -
Virginia Martín-Nieves,
Carme Fàbrega,
Marc Guasch,
Susana Fernández,
Yogesh S. Sanghvi,
Miguel Ferrero,
Ramón Eritja
Publication year - 2021
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.0c00717
Subject(s) - chemistry , oligonucleotide , conjugate , anomer , combinatorial chemistry , protecting group , sugar , stereochemistry , oligonucleotide synthesis , biochemistry , organic chemistry , gene , mathematical analysis , alkyl , mathematics
Oligonucleotide conjugates are widely used as therapeutic drugs, gene analysis, and diagnostic tools. A critical step in the biologically relevant oligonucleotide conjugates is the design and synthesis of functional molecules that connect oligonucleotide with ligands. Here, we report the synthesis and application for oligonucleotide functionalization of novel tethers based on aminomethyl and mercaptomethyl sugar derivatives. Starting from a common cyano sugar precursor, three novel phosphoramidites have been prepared in the two α- and β-anomeric forms. The mercaptomethyl sugar was protected with the S -acetyl group, while two different protecting groups have been developed for the aminomethyl sugar. These two protecting groups are orthogonal, as they can be removed independently using photolysis or ammonolysis. This combination allowed the introduction of two different ligands in a single oligonucleotide.