New developments in the synthesis of oligonucleotide-peptide conjugates

The stability of oligodeoxynucleotides to trifluoroacetic acid is studied. Pyrimidine oligonucleotides were stable in the conditions used for the removal of t-butyl groups. Oligonucleotide-3′-peptide conjugates carrying pyrimidine oligonucleotides are prepared stepwise using peptide-supports and Fmoc, t-butyl strategy. Using this strategy we have prepared an oligonucleotide-peptide conjugate containing as peptide the leucine-rich fragment of FOS, a transcription factor involved in many important cellular processes. This conjugate has a long peptide sequence with a large number of trifunctional amino acids.Project financed by Spanish Ministry of Education SAF2004-01044, BFU2005-23719- E, NAN2004-09415-C05-03 and BFU2004-02048. C. P. thanks the Spanish Ministry for a predoctoral fellowship.Peer reviewe