The crystal structure of a decameric HNA/RNA (HNA = 2`,3`-dideoxy-l`,5`-anhydro-D-arabinohexitol nucleic acid) hybrid with the RNA sequence 5`-GGCAUUACGG-3` is the first crystal structure of a hybrid duplex between a naturally occurring nucleic acid and a strand, which is fully modified to contain a six-membered ring instead of ribose. The presence of four duplex helices in the asymmetric unit allows for a detailed discussion of hydration, which revealed a tighter spinelike backbone hydration for the HNA than for the RNA-strands. The reinforced backbone hydration is suggested to contribute significantly to the exceptional stability of HNA-containing duplexes and might be one of the causes for the evolutionary preference for ribose-derived nucleic acids.
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