Stability of the pH-Dependent Parallel-Stranded d(CGA) Motif
| Autor: | Emily M. Luteran, Jason D. Kahn, Paul J. Paukstelis |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
endocrine system
Stereochemistry Oligonucleotides Biophysics Ph dependent Antiparallel (biochemistry) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine DNA nanotechnology Structural motif Base Pairing 030304 developmental biology 0303 health sciences Nuclease biology Oligonucleotide DNA Articles Hydrogen-Ion Concentration chemistry Duplex (building) biology.protein Nucleic Acid Conformation Chemical stability 030217 neurology & neurosurgery |
| Zdroj: | Biophys J |
| ISSN: | 0006-3495 |
| Popis: | Non-canonical DNA structures that retain programmability and structural predictability are increasingly being used in DNA nanotechnology applications, where they offer versatility beyond traditional Watson-Crick interactions. The d(CGA) triplet repeat motif is structurally dynamic and can transition between parallel-stranded homo-base paired duplex and anti-parallel unimolecular hairpin in a pH-dependent manner. Here, we evaluate the thermodynamic stability and nuclease sensitivity of oligonucleotides composed of the d(CGA) motif and several structurally related sequence variants. These results show that the structural transition resulting from decreasing the pH is accompanied by both a significant energetic stabilization and decreased nuclease sensitivity as unimolecular hairpin structures are converted to parallel-stranded homo-base paired duplexes. Furthermore, the stability of the parallel-stranded duplex form can be altered by changing the 5′-nucleobase of the d(CGA) triplet and the frequency and position of the altered triplets within long stretches of d(CGA) triplets. This work offers insight into the stability and versatility of the d(CGA) triplet repeat motif and provides constraints for using this pH-adaptive structural motif for creating DNA-based nanomaterials.STATEMENT OF SIGNIFICANCEThis article addresses the stability of the d(CGA) triplet motif and variants in solution. Our study reveals changes in thermodynamic stability and nuclease resistance in response to pH. The identity of the 5′-nucleobase within each triplet and the position and frequency of different triplets within stretches of d(CGA) triplets can tune parallel-stranded duplex stability. This tunability can be used for nanotechnological applications where the specificity of the 5′-nucleobase pairing interaction is used to order of long stretches of d(CGA) triplets. These results can inform the rational design of pH-sensitive structurally switchable DNA-based nanomaterials. |
| Databáze: | OpenAIRE |
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