Synthesis of peptide-oligonucleotide conjugates using a heterobifunctional crosslinker

Berea A R Williams, John C. Chaput

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Peptide-oligonucleotide conjugates (POCs) are molecular chimeras composed of a nucleic acid moiety covalently attached to a polypeptide moiety. POCs have been used in numerous applications from therapeutics to nanotechnology, and most recently as combinatorial agents in the assembly of bivalent protein affinity reagents. This unit describes the synthesis and purification of POC molecules using the heterobifunctional crosslinking reagent succinimidyl-4-(N- maleimidomethyl)cyclohexane-1-carboxylate (SMCC), which enables amine-modified oligonucleotides to become covalently linked to cysteine-modified polypeptides. This solution-based protocol consists of a two-step synthesis followed by a single purification step.

Original languageEnglish (US)
Pages (from-to)4.41.1-4.41.20
JournalCurrent Protocols in Nucleic Acid Chemistry
Issue numberSUPPL. 42
StatePublished - 2010


  • DNA nanotechnology
  • antisense
  • fragment conjugation
  • nanodisplay
  • peptide-oligonucleotide conjugate
  • succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC)
  • synbodies

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry


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