Marcel Chassignol

Solid-phase preparation of 5′,3′-heterobifunctional oligodeoxyribonucleotides using modified solid supports

Abstract The solid-phase preparation of oligodeoxyribonucleotides attached to intercalator or reactive groups through their 5′- and (or) 3′-ends is reported. These syntheses implicate the introduction of suitable masked functional groups at the 5′-end of the oligonucleotide by the intermediate of their phosphoramidite derivatives or at the 3′-end of the oligonucleotide using modified solid supports. After full deblocking, the functional groups (phosphate, thiophosphate, primary amine or thiol) can be reacted with the suitable reactive group involved in the chosen ligand. These methods allow the preparation of heterobifunctional derivatized oligodeoxyribonucleotides.

Solid phase synthesis of oligo-α- and oligo-β-deoxynucleotidescovalently linked to an acridine

Abstract Oligo-α- and oligo-β-deoxynucleotides covalently linked at their 5′- end to an intercalating agent are synthesized on an automatic solid-phase DNA synthesizer. The acridine group was introduced with the acridine-phosphoramidite 5 , easily obtained from 2-methoxy-6-chloro-9-(ω-hydroxypentylamino)acridine 4 and 2-cyanoetyl N,N,N′,N′-tetraisopropyl-phosphoro-diamidite. The oligomers from the matrix were cleaved and unblocked in one step by sodium hydroxide.

Synthese et reactivite d'oligothymidylates substitues par un agent intercalant et un groupe thiophosphate

Abstract An acridine dye derivative and a thiophosphate group have been covalently tethered to both ends of oligothymidylates. The sulphur atom of the thiophosphate anion reacts specifically with electrophilic agents, thereby allowing a variety of other chemical species to be attached to the modified oligonucleotides.

Synthesis and structural studies of a self-complementary decadeoxynucleotide d(AATTGCAATT) II. - Proton magnetic resonance studies

Proton magnetic resonance spectra of the self-complementary decadeoxynucleotide d(AATTGCAATT) at 90 and 250 MHz have been obtained at different temperatures. The assignment of the different resonance lines to the base protons was obtained by combining the data derived from various methods: hydrogen in equilibrium with deuterium exchange at the H8 position of purines; comparison of NMR spectra obtained at high temperature with those of mononucleotides; comparison of the variations in chemical shifts obtained between 280 K and 360 K with calculated values; determination of half-transition temperatures for each base pair. On the basis of computed chemical shifts for stacked base-pairs it is concluded that the decadeoxynucleotide duplex exists in the B form in solution at 280 K. Propagation of the opening of the mini double helix from terminal to central base pairs if reflected in the variation of half-transition temperatures which vary between 306 K and 327 K.