Chemistry of Peptide-Oligonucleotide Conjugates: A Review

Molecules

Dmitry Stetsenko¹  Alesya Fokina¹  Kristina Klabenkova¹ 

[1] Faculty of Physics, Novosibirsk State University, 630090 Novosibirsk, Russia;

关键词: cell-penetrating peptide;    nucleic acid therapeutic;    antisense oligonucleotide;    small interfering RNA (siRNA);    peptide nucleic acid (PNA);    locked nucleic acid (LNA);   

DOI  :  10.3390/molecules26175420

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown