Chemistry of peptide-oligonucleotide conjugates: A review

Kristina Klabenkova, Alesya Fokina, Dmitry Stetsenko

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Article number5420
JournalMolecules
Volume26
Issue number17
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Antisense oligonucleotide
  • Cell-penetrating peptide
  • Cellular uptake
  • Click chemistry
  • Drug delivery
  • Locked nucleic acid (LNA)
  • Nucleic acid therapeutic
  • Peptide nucleic acid (PNA)
  • Phosphordiamidate morpholino oligomer (PMO)
  • Small interfering RNA (siRNA)

OECD FOS+WOS

  • 3.01 BASIC MEDICAL RESEARCH
  • 1.04 CHEMICAL SCIENCES
  • 1.06.CQ BIOCHEMISTRY & MOLECULAR BIOLOGY

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