title: Synthesis and hybridization properties of oligonucleotides containing polyamines at the C-2 position of purines: a pre-synthetic approach for the incorporation of spermine into oligodeoxynucleotides containing 2-(4,9,13-triazatridecyl)-2'-deoxyguanosine.
abstract: We have developed a synthesis of spermine-containing oligonucleotides (ODN-sper) which allows incorporation of multiple polyamine residues. This approach was based on the pertrifluoroacetylated 5'DMT-dGsper phosphoramidite synthon. Its coupling yield with resin-bound ODN decreased dramatically when close to the 3'-end. Optimization of the coupling conditions allowed 22-mer ODNs containing up to six spermine residues to be synthesized. Several ODNs of different sequences with 1-4 pendent spermines could be purified and their hybridization properties were evaluated. Duplex melting temperatures increased linearly with the number of polyamine residues (deltaTm/sper = 3.0 +/- 0.2 degrees C in 100mM NaCl). This compares very favorably with values reported for duplexes of similar initial stability containing other cation-substituted bases. Moreover, the stability increase was neither sequence nor position-dependent, and even contiguous spermine residues did not cross-talk. Extrapolation based on these findings leads to the conclusion that a duplex formed with a 22-mer oligonucleotide containing seven spermine residues would be as stable as genomic DNA, which highlights its potential for DNA strand invasion.
authors: Laboratoire de Chimie Génétique associé CNRS, Université Louis Pasteur de Strasbourg, Illkirch, France.
authors: P
authors: P
authors: Potier
authors: A
authors: A
authors: Abdennaji
authors: J P
authors: JP
authors: Behr
mesh_terms: D001372:Aza Compounds / Q000737:chemistry*; D001483:Base Sequence; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013096:Spermine / Q000032:analysis*
chemical_list: C419107:2-(4,9,13-triazatridecyl)-2'-deoxyguanosine; D001372:Aza Compounds; D009841:Oligonucleotides; D013096:Spermine; D003849:Deoxyguanosine