Chemistry of Peptide-Oligonucleotide Conjugates: A Review

Peptide-oligonucleotide conjugates (POCs) represent one of the increasingly successful albeit costly approaches to increasing cellular uptake, tissue delivery, bioavailability, and, thus, overall efficiency therapeutic nucleic acids, such as, antisense oligonucleotides and small interfering RNAs. This review puts subject chemical synthesis POCs into wider context problem acid drug cell-penetrating peptide structural types, mechanisms their intracellular transport, ways application, which include formation non-covalent complexes with (peptide additives) or covalent conjugation. The main strategies for are viewed in detail, conceptually divided (a) stepwise solid-phase approach (b) post-synthetic conjugation either solution on solid phase, especially by means various click chemistries. relative advantages disadvantages both discussed compared.