Academic Journal
Comparison of the Thermodynamics and Base-Pair Dynamics of a Full LNA:DNA Duplex and of the Isosequential DNA:DNA Duplex
| Title: | Comparison of the Thermodynamics and Base-Pair Dynamics of a Full LNA:DNA Duplex and of the Isosequential DNA:DNA Duplex |
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| Authors: | Bruylants, Gilles, Boccongelli, Marina, Snoussi, Karim, Bartik, Kristin |
| Source: | Biochemistry, 48 (35 |
| Publisher Information: | American Chemical Society (ACS), 2009. |
| Publication Year: | 2009 |
| Subject Terms: | 0301 basic medicine, 0303 health sciences, Molecular Structure, Circular Dichroism, Nucleic Acid Heteroduplexes, Oligonucleotides, Nucleic Acid Hybridization, Chemical, DNA, Sciences de l'ingénieur, Oligonucleotides -- chemistry, Nucleic Acid Heteroduplexes -- chemistry, 03 medical and health sciences, Models, Chemical, Models, Circular Dichroism -- methods, DNA -- chemistry, Chimie, Nucleic Acid Conformation, Thermodynamics, Thermodynamique chimique, Base Pairing |
| Description: | Locked nucleic acids (LNA), conformationally restricted nucleotide analogues, are known to enhance pairing stability and selectivity toward complementary strands. With the aim to contribute to a better understanding of the origin of these effects, the structure, thermal stability, hybridization thermodynamics, and base-pair dynamics of a full-LNA:DNA heteroduplex and of its isosequential DNA:DNA homoduplex were monitored and compared. CD measurements highlight differences in the duplex structures: the homoduplex and heteroduplex present B-type and A-type helical conformations, respectively. The pairing of the hybrid duplex is characterized, at all temperatures monitored (between 15 and 37 degrees C), by a larger stability constant but a less favorable enthalpic term. A major contribution to this thermodynamic profile emanates from the presence of a hairpin structure in the LNA single strand which contributes favorably to the entropy of interaction but leads to an enthalpy penalty upon duplex formation. The base-pair opening dynamics of both systems was monitored by NMR spectroscopy via imino protons exchange measurements. The measurements highlight that hybrid G-C base-pairs present a longer base-pair lifetime and higher stability than natural G-C base-pairs, but that an LNA substitution in an A-T base-pair does not have a favorable effect on the stability. The thermodynamic and dynamic data confirm a more favorable stacking of the bases in the hybrid duplex. This study emphasizes the complementarities between dynamic and thermodynamical studies for the elucidation of the relevant factors in binding events. |
| Document Type: | Article |
| File Description: | 2 full-text file(s): application/pdf; application/pdf |
| Language: | English |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi900615z |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/19670874 https://pubmed.ncbi.nlm.nih.gov/19670874/ https://www.ncbi.nlm.nih.gov/pubmed/19670874 https://difusion.ulb.ac.be/vufind/Record/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/54636/Details https://pubs.acs.org/doi/abs/10.1021/bi900615z https://dial.uclouvain.be/pr/boreal/object/boreal:35339 https://pubs.acs.org/doi/10.1021/bi900615z http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/54636 |
| Accession Number: | edsair.doi.dedup.....68f07b492f93b35d253fde4b8cf94797 |
| Database: | OpenAIRE |
| ISSN: | 15204995 00062960 |
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| DOI: | 10.1021/bi900615z |