9F3D

Single acyclic phosphonate nucleotide (S)-ZNA modification on DNA hairpin

Summary for 9F3D

• Entry DOI: 10.2210/pdb9f3d/pdb
• NMR Information: BMRB: 34914
• Descriptor: C modifed (S)-ZNA (1 entity in total)
• Functional Keywords: xna, dickerson drew decamers, (s)-zna, acyclic backbone, phosphonate linkage, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 3635.38

Authors

Li, X.,Groaz, E.,Herdewijn, P.,Lescrinier, E. (deposition date: 2024-04-25, release date: 2024-06-05, Last modification date: 2024-07-10)

Primary citation

Li, X.,Groaz, E.,Herdewijn, P.,Lescrinier, E.
Impact of Single Acyclic Phosphonate Nucleotide (ZNA) Modifications on DNA Duplex Stability.
Chemistry, 30:e202401254-e202401254, 2024

PubMed Abstract: An acyclic phosphonate-linked nucleic acid backbone (ZNA) demonstrated the capability to support duplex formation and propagate genetic information in vivo, unveiling its potential for evolution into a synthetic genetic system (XNA). To determine the structural impact of such modification, modified Dickerson Drew DNA dodecamers (DDDs) were prepared by solid phase synthesis, each containing either an (R) or (S) isomeric form of a cytosine ZNA nucleotide. While the DDD is known to adopt a stable duplex, both duplex and hairpin forms were simultaneously observed for both modified oligonucleotides by NMR spectroscopy over a broad temperature range (5-65 °C). Diffusion-ordered spectroscopy (DOSY) experiments allowed to separate duplex and hairpin signals based on the different diffusion constants of both conformational states. For the oligomer containing (R)-ZNA, only the duplex form occurred at 5 °C, while it was not possible to determine by NMR a single hairpin conformation at higher temperatures. In the case of the (S)-ZNA nucleoside modified oligomer, both hairpin and duplex forms were observable at 0 °C, while a single hairpin conformation was detected at 37 °C, suggesting a higher destabilizing effect on dsDNA.

PubMed: 38687344
DOI: 10.1002/chem.202401254

Experimental method

SOLUTION NMR