Synthesis and properties of oligo-2'-deoxyribonucleotides containing internucleotidic phosphoramidate linkages modified with pendant groups ending with either two amino or two hydroxyl functions.
Single and multiple incorporations of stereochemically pure modified dinucleoside-phosphoramidates involving substituent groups ending with bis-hydroxyethyl and bis-aminoethyl groups have been performed into pyrimidic triple helix-forming oligo-2'-deoxyribonucleotides designed to bind parallel to the purine strand of the DNA target. The ability of these modified oligo-2'-deoxyribonucleotides to form triple helices has been studied by UV-melting curve analyses, and circular dichroism. Only the oligonucleotides involving modified phosphate groups with the Rp configuration formed more stable triple helices than did the parent phosphodiester sequences. Incorporating the modifications into the third oligonucleotide strands has little effect on the structure of the triplexes. At pH 7, the incorporation of two, three or four modified phosphate groups into the third strands stabilizes the triplexes, as compared to the unmodified oligonucleotide. Stronger stabilization was observed with compounds containing linkers ending with amino functions. Stability increases with the number of modifications without being fully additive. This might be due to the different environments of the phosphate groups inside the sequence.
Asseline
Ulysse
U
Centre de Biophysique Moléculaire, CNRS UPR 4301, affiliated with the University of Orléans and with INSERM, Rue Charles Sadron, 45071 Cedex 02, Orléans, France. asseline@cnrs-orleans.fr
Chassignol
Marcel
M
Draus
Jolanta
J
Durand
Maurice
M
Maurizot
Jean Claude
JC
D000577:Amides / Q000737:chemistry*; D001483:Base Sequence; D002942:Circular Dichroism; D003854:Deoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D006900:Hydroxylation; D007536:Isomerism; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation / Q000528:radiation effects; D010756:Phosphoric Acids / Q000737:chemistry*; D013053:Spectrophotometry; D044366:Transition Temperature; D014466:Ultraviolet Rays
D000577:Amides; D003854:Deoxyribonucleotides; D010756:Phosphoric Acids; C011067:phosphoramidic acid