Sequence specific hybridization properties of methylphosphonate oligodeoxynucleotides

Methylphosphonate oligodeoxynucleotides (MPO's) with isomerically pure Rp-configurated methylphosphonates (MP's) were synthesized by block coupling of ApT and TpA dinucleoside methylphosphonates (DMP's, p indicating MP-linkage). Oligonucleotide duplexes (20 mers) with these Rp-MP's showed almost the same melting temperatures (Tm) as those with phosphorodiester bonds. Further a dependence of the duplex stability from the nucleosides (bases) adjacent to the MP moiety was observed. For the first time thermodynamic parameters for the duplex to coil transition of isomerically pure MP's were determined from the concentration dependence of the Tm. CD-spectra of the duplexes show structural changes which can be associated with the transition to a compact helix with higher helix winding angle.