Chemical conjugations of post-synthetic nucleic acids with macromolecules or small tag molecules are a common strategy to study nucleic acids in chemistry and biology, and to exploit nucleic acids for medical applications. For example, conjugations of nucleic acids such as siRNA, miRNA and antisense DNA oligonucleotides with peptides to acquire peptide-oligonucleotide conjugates (POCs) is especially attractive for circumventing cell delivery and specificity problems of nucleic acids as therapeutic agents. Recently, my research group has developed the phosphoramidation reaction method for effective POC synthesis (Wang et al., 2010, Bioconjugate Chem. 21, 1642; Wang et al., 2012, Bioconjugate Chem., 23, 2417). Here we explore chemistry of the nucleic acid phosphoramidation reactions and applications of the reactions for post-synthetic nucleic acid conjugation and labeling essential to chemical and biological studies of DNA/RNA (Su et al., 2014, Anal. Biochem., 449, 118). When integrated with bioorthogonal reactions such as biocompatible click chemistry and strain-promoted azide-alkyne cycloaddition, the phosphormaidation reactions could be an even more powerful approach for nculeic acid modifications, including synthesis of POCs for traget delivery of nucleic acids in biological systems (Su et al., 2014, Org. Biomol. Chem., 12, 6624). We are expecting that the nucleic acid phosphoramidation reactions will have broader applications in fundamental research and clinical administrations.

Phosphoramidation-based bioorthogonal reactions for synthesis of nucleic acid conjugates potentially useful in target delivery of DNA/RNA therapeutics

249th National Meeting (2015)

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