The Assembly of Fluorescently Labeled Peptide–Oligonucleotide Conjugates via Orthogonal Ligation Strategies
Efficient intracellular delivery is critical to the successful application of synthetic antisense oligonucleotides (ASOs) to modulate gene expression. The conjugation of cell-penetrating peptides (CPPs) to ASOs has been shown to significantly improve their intracellular delivery. It is important, however, that formation of the covalent linkage between the peptide and oligonucleotide is efficient and orthogonal, to ensure high yields and a homogeneous product. Described herein are efficient and facile methodologies for the conjugation of peptides to ASOs, and their subsequent labeling with various moieties such as fluorescent dyes for intracellular tracking studies.
Key wordsPeptides Oligonucleotides Conjugation Fluorescent labeling Alkyne–azide
This work was supported by MND Research Institute of Australia (MNDRIA GIA-1722), National Health and Medical Research Council (Project Grant 1104299), and the Stafford Fox Medical Research Foundation.
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