The synthesis of 4′-methoxymethyl threofuranosyl (4′-MOM-TNA) thymidine and derived oligomers of the G-rich thrombin-binding aptameric (TBA) sequence is reported. The G-quadruplex stability, anticoagulation activity, and the enzymatic stability of these oligomers bearing the 2′-3′-phosphodiester backbone as single substitutions in the loop regions are studied. Amongst all the oligomers, TBA-7T bearing the 4′-MOM-TNA unit at the T7 position formed a quadruplex with the highest thermal stability. It also resulted in enhanced anticlotting activity that allowed a one-third reduction in the dose, relative to TBA. Further, TBA-7T exhibited enhanced nuclease resistance properties to both endo- and exonucleases.

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The chemical reasoning would suggest that Ene-nucleic acid precursors with constrained flexibility and selectivity could be the missing link between the prochiral-acyclic and chiral-cyclic structures.

3'-5'-Deoxyribose-sugar-phoshate backbone in DNA is completely replaced by 2'-deoxyribonucleoside-based β-amino acids interlinked by glycine to create uncharged polyamide DNA with 3'-5'-directionality. These oligomers as conjugates of α-amino acids and nucleoside-β-amino acids bind strongly and sequence-specifically only to the antiparallel complementary RNA and DNA.