Diels-Alder cycloadditions in water for the straightforward preparation of peptide-oligonucleotide conjugates.
The Diels-Alder reaction between diene-modified oligonucleotides and maleimide-derivatized peptides afforded peptide-oligonucleotide conjugates with high purity and yield. Synthesis of the reagents was easily accomplished by on-column derivatization of the corresponding peptides and oligonucleotides. The cycloaddition reaction was carried out in mild conditions, in aqueous solution at 37 degrees C. The speed of the reaction was found to vary depending on the size of the reagents, but it can be completed in 8-10 h by reacting the diene-oligonucleotide with a small excess of maleimide-peptide.
Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, E-08028, Barcelona, Spain. vmarchan@ub.edu
Vicente
V
Marchán
Samuel
S
Ortega
Daniel
D
Pulido
Enrique
E
Pedroso
Anna
A
Grandas
D000595:Amino Acid Sequence; D008301:Maleimides / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D008301:Maleimides; D009841:Oligonucleotides; D020135:Peptide Nucleic Acids; D010455:Peptides; D014867:Water