ArticleProceedings of the National Academy of Sciences of the United States of America2026
Hydrophobic unnatural base pair promotes trigger loop closure and catalysis in cellular RNA polymerase independent of hydrogen bonding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Expanded genetic alphabets based on synthetic nucleotides offer a powerful strategy to increase the chemical diversity and functional potential of nucleic acids. Hydrophobic unnatural base pairs (UBPs) represent a unique class of UBPs that operate without canonical hydrogen bonding and shapes, which are distinct from natural base pairs. However, the molecular mechanisms governing hydrophobic UBP recognition and incorporation by RNA polymerases remain poorly understood, because no structures of catalytically competent state have been captured. Here, we investigate the enzyme kinetics and structural basis of transcription recognition of hydrophobic 7-(2-thienyl)-imidazo[4,5-b]pyridine (Ds):pyrrole 2-carbaldehyde (Pa) base pair by the
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