Solid-phase synthesis of oligopurine deoxynucleic guanidine (DNG) and analysis of binding with DNA oligomers

Abstract

The first stepwise solid-phase synthesis of deoxynucleic guanidine (DNG), a positively charged DNA analog, using controlled pore glass as the solid support is reported. For the first time, purine bases have been incorporated into the DNG oligomer and DNG has been synthesized using a solid-phase method, proceeding in the 3'-->5' direction, that is compatible with the cleavage conditions used in the solid-phase synthesis of DNA. A DNG sequence containing a pentameric tract of adenosine nucleosides has been synthesized and the thermal denaturation temperature of its complexes with complementary thymidyl DNA oligomers was 79 degrees C. Binding of thymidyl DNA oligomers to adenyl DNG oligomers is 2:1, as seen in thymidyl and adenyl DNA triplexes. No binding of adenyl DNG with octameric cytidyl DNA was observed, indicating that the positive charge does not overcome base pairing fidelity.

Is there a common chemical model for life in the universe?

“…The DNA duplex, where a polyanion binds another polyanion, appears to disregard Coulomb's law. One might think (and indeed, many have thought) [81,82] that the duplex would be more stable if one strand were uncharged, or polycationic [83,84].…”

Novel and efficient syntheses of 3′,5′-diamino derivatives of 2′,3′,5′-trideoxycytidine and 2′,3′,5′-trideoxyadenosine. Protonation behavior of 3′,5′-diaminonucleosides

“…N 6 -Benzoyl-3',5'-di-O-methanesulfonyl-2'-deoxyxyloadenosine (10). DMAP (688 mg, 5.63 mmol) was added to a solution of compound 9 (200 mg, 0.56 mmol) in dry pyridine (8 mL) 16 A solution of compound 11 (50 mg, 0.12 mmol) in EtOH (4 mL) was exposed to a positive pressure of hydrogen gas (balloon) at room temperature for 4 h in the presence of Pd black (20 mg). The catalyst was removed by filtration on Celite and the filtrate was evaporated to dryness.…”

ChemInform Abstract: From Anionic to Cationic α‐Anomeric Oligodeoxynucleotides

“…Enhancing the stability of oligonucleotide -RNA hybrids is also useful to sterically block the RNA translation. Best examples supporting this concept are ODNs bearing 5-(aminoprop-1ynyl) deoxyuridines instead of thymidines [148] [149], sugar-modified 2'-O-(2-aminoethyl) ODNs [150] [151], and dephospho deoxynucleic guanidine (DNG) [152] [153]. However, introduction of positives charges does not lead to the expected enhanced hybridization at any time.…”

“…For instance, the singular behavior of deoxynucleic guanidine (DNG; Fig. 15) [152] [153] towards hybridization results from Coulombic (electrostatic) interactions without saltbridge formation between positively and negatively charged backbones. For b-ODNs containing 5-(aminoprop-1-ynyl) deoxyuridines [148] [149], the amino group of the modified base does not interact with the phosphates of the target but with the phosphates of the modified ODN itself, preorganizing the ODN for hybridization.…”