2KK5

High Fidelity Base Pairing at the 3'-Terminus

Summary for 2KK5

• Entry DOI: 10.2210/pdb2kk5/pdb
• Descriptor: 5'-D(*AP*CP*GP*CP*GP*(2AU))-3', 9,10-dioxo-9,10-dihydroanthracene-2-carboxamide (2 entities in total)
• Functional Keywords: anthraquinone-linked dna, dna
• Total number of polymer chains: 2
• Total formula weight: 4122.89

Authors

Patra, A.,Richert, C. (deposition date: 2009-06-15, release date: 2009-07-21, Last modification date: 2024-05-22)

Primary citation

Patra, A.,Richert, C.
High fidelity base pairing at the 3'-terminus.
J.Am.Chem.Soc., 131:12671-12681, 2009

PubMed Abstract: Binding target strands with single base selectivity at a terminal position is difficult with natural DNA or RNA hybridization probes. Nature uses a degenerate genetic code that is based on RNA:RNA codon:anticodon duplexes tolerating wobble base pairs at the terminus. The importance of short RNA strands in regulatory processes in the cell make it desirable to develop receptor-like approaches for high fidelity binding, even at the very 3'-terminus of a probe. Here, we report the three-dimensional structure of a DNA duplex with a 3'-terminal 2'-anthraquinoylamido-2'-deoxyuridine (Uaq) residue that was solved by NMR and restrained molecular dynamics. The Uaq residue binds the 5'-terminus of the target strand through a combination of pi-stacking, hydrogen bonding, and interactions in the minor groove. The acylated aminonucleoside is the best molecular cap for 3'-termini reported to date. The Uaq motif assists binding of DNA strands, but is particularly effective in enhancing the affinity for RNA target strands, with a DeltaT(m) in the UV melting point of up to +18.2 degrees C per residue. Increased base pairing selectivity is induced for all sequence motifs tested, even in cases where unmodified duplexes show no preference for the canonical base pair at all. A single mismatched nucleobase facing the 3'-terminus gives DeltaDeltaT(m) values as large as -23.9 degrees C (RNA) or -29.5 degrees C (DNA). The 5'-phosphoramidite of the Uaq cap reported here allows for routine incorporation during automated syntheses.

PubMed: 19722718
DOI: 10.1021/ja9033654

Experimental method

SOLUTION NMR