Efficient Synthesis of 2'-O-Methoxyethyl Oligonucleotide-Cationic Peptide Conjugates.

ABSTRACT: Single-stranded phosphorothioate (PS) oligonucleotide drugs have shown potential for the treatment of several rare diseases. However, a barrier to their widespread use is that they exhibit activity in only a narrow range of tissues. One way to circumvent this constraint is to conjugate them to cationic cell-penetrating peptides (CPPs). Although there are several examples of morpholino and peptide nucleic acids conjugated with CPPs, there are noticeably few examples of PS oligonucleotide-CPP conjugates. This is surprising given that PS oligonucleotides presently represent the largest class of approved RNA-based drugs, including Nusinersen, that bears the 2'-O-methoxyethyl (MOE)-chemistry. In this work, we report a method for in-solution conjugation of cationic, hydrophobic peptides or human

SUBMITTER: Halloy F 

PROVIDER: S-EPMC9291120 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature