Expanded genetic alphabet increases structural and chemical diversity of six-letter DNA for high-affinity protein-targeting aptamers.

ABSTRACT: Expanding the genetic alphabet through unnatural base pairs (UBPs) enables the creation of novel biopolymers with enhanced informational and functional properties. Hydrophobic UBPs, such as Ds-Px/Pa', exhibit high fidelity during PCR, facilitating the evolutionary engineering of UB-containing DNA aptamers (XenoAptamers) with exceptional target affinity and specificity. A series of XenoAptamers targeting dengue non-structural protein 1 (NS1), a key biomarker for dengue infection, can distinguish subtle amino acid differences among NS1 variants beyond serotypes. However, the molecular basis of this remarkable specificity and affinity remained unclear. Here, we determine cryo-EM structures of NS1-XenoAptamer complexes. Each XenoAptamer adopts a unique stable tertiary structure that precisely

SUBMITTER: Sawada K 

PROVIDER: S-EPMC12824200 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature