Unit

UNIT 4.32 Synthesis of Peptide-Oligonucleotide Conjugates by Diels-Alder Cycloaddition in Water

  1. Vicente Marchán,
  2. Anna Grandas

Published Online: 1 DEC 2007

DOI: 10.1002/0471142700.nc0432s31

Current Protocols in Nucleic Acid Chemistry

Current Protocols in Nucleic Acid Chemistry

How to Cite

Marchán, V. and Grandas, A. 2007. Synthesis of Peptide-Oligonucleotide Conjugates by Diels-Alder Cycloaddition in Water. Current Protocols in Nucleic Acid Chemistry. 31:4.32:4.32.1–4.32.31.

Author Information

  1. Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain

Publication History

  1. Published Online: 1 DEC 2007
  2. Published Print: DEC 2007

Abstract

Peptide-oligonucleotide conjugates incorporating all the nucleobases and trifunctional amino acids are obtained by Diels-Alder reaction between diene-modified oligonucleotides (2′-deoxyribo- or ribo-) and malemide-derivatized peptides. Both reagents are easily synthesized by on-column derivatization of the corresponding peptides and oligonucleotides. The cycloaddition reaction is carried out under mild conditions, in aqueous solution at 37°C, affording the desired peptide-oligonucleotide conjugate with high purity and yield. The speed of the reaction depends on the size and composition of both reagents, but it is accelerated by the presence of positively charged amino acids in the peptide fragment. However, a small excess of maleimide-derivatized peptide may be required in some cases to complete the reaction within 8 to 10 hr. Curr. Protoc. Nucleic Acid Chem. 31:4.32.1-4.32.31. © 2007 by John Wiley & Sons, Inc.

Keywords:

  • peptide-oligonucleotide conjugate;
  • Diels-Alder cycloaddition;
  • oligonucleotide synthesis;
  • peptide synthesis