Base‐Pairing Properties of Double‐Headed Nucleotides

Abstract

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Double‐Headed Nucleotides with Non‐Native Nucleobases: Synthesis and Duplex Studies

“…For instance, when central 5'-UC or 5'-UG dinucleotides are replaced with the U C or U G double-headed nucleotide monomers, respectively, the thermal duplex stability remains intact ( Figure 1, green bars). [25] The 2'-bases of U C and U G also display a good mismatch discrimination comparable to that of mismatches involving natural nucleotides (Figure 1, white bars). When U T and U A monomers are incorporated, the duplex is slightly destabilized by 2.5°C to 3.5°C.…”

“…Currently, the full set of uridine-based analogues (U C , U G , U T , U A ) have been presented and evaluated together with selected cytosine-and adenosine-based analogues in the form of C C and A T . [23][24][25][26][27] These double-headed nucleotides are wellaccommodated in DNA duplexes when incorporated in exchange for the corresponding dinucleotide ( Figure 1). For instance, when central 5'-UC or 5'-UG dinucleotides are replaced with the U C or U G double-headed nucleotide monomers, respectively, the thermal duplex stability remains intact ( Figure 1, green bars).…”

“…In practice, it can form two sets of Watson-Crick base pairs with two individual nucleotides of the opposite strand: one through its 1'-base to give a 1'•1' base pair, and another through its 2'-base to give a 2'•1' base pair. [24][25][26] This feature allows for the condensation of genetic information to smaller entities with fewer phosphates, which might be an effective approach for e. g. enhancing cellular uptake or target recognition in future nucleic acid-based therapeutics.…”

“…When U T and U A monomers are incorporated, the duplex is slightly destabilized by 2.5°C to 3.5°C. [25,27] While the 2'•1' mismatch discrimination capacity of U T and U A against T, A or C also resemble those of the unmodified duplexes, the discrimination against G is insufficient (1.0-1.5°C). Therefore, U T and U A analogs with increased 2'-specificity are of interest.…”

“…Nevertheless, C was found to be only marginally discriminated (1.0°C) when U H is used ( Figure 1). [25] In this report, we present the synthesis and evaluation of a new double-headed nucleotide monomer (U Z ) containing 5aza-7-deazaxanthine (Z) in the 2'-position. This purine nucleobase has been introduced into natural 2'-deoxynucleotides by Dea and co-workers, [30] and later explored by the Benner group aiming for alternative DNA base pairs.…”