Dynamic combinatorial chemistry (DCC) has emerged as a powerful tool for screening and optimization of lead compounds for the discovery of new drugs. This thesis introduces a novel method for base filling through the reversible incorporation of nucleobase aldehydes into the backbone of modified oligonucleotides using the principle of DCC. The formation of N-methoxy-1,3-oxazinane (MOANA) and N-methoxy-1,3-oxazolidine (MOGNA) nucleoside analogues for the preparation of oligonucleotide conjugates has been systematically studied. The reaction involves the unprotected (2R,3S)-4-(methoxyamino)butane-1,2,3-triol (MABT) residue and nucleobase modified aldehydes. The reaction is reversible under slightly acidic conditions (pH 5.5) and affords highly stable products at pH 7.4, where the reaction effectively enters a "switched-off" state. The reaction rates and equilibrium constants were influenced by the structural variations of the aldehydes with observed half-lives (t₁/₂) ranging from 9 to 32 hours. The reaction was predominantly driven by base stacking interactions and demonstrated significantly higher yield and base-pairing selectivity within the relatively rigid A-type double helices compared to the more flexible B-type double helices. In contrast, both single-stranded oligonucleotides and the Hoogsteen strand of triple helices exhibited significantly lower yield and selectivity for base-filling. The effects of the two isomers of the (2R,3S)-4-(methoxyamino)butane-1,2,3-triol scaffold on base-pairing selectivity were modest and varied depending on the sequence. This work is promising for the development of a modified oligonucleotides scaffold for reversible base filling which is important for the development of oligonucleotide therapeutics, diagnostics and DNA nanotechnology.