Complete mesoscopic parameterization of single LNA modifications in DNA applied to oncogene probe design

Página do item simplificado
dc.creatorIzabela Ferreira da Silva
dc.creatorSofie Slott
dc.creatorKira Astakhova
dc.creatorGerald Weber
dc.date.accessioned2025-02-24T17:54:12Z
dc.date.accessioned2025-09-09T01:08:50Z
dc.date.available2025-02-24T17:54:12Z
dc.date.issued2021
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.identifier.doihttps://doi.org/10.1021/acs.jcim.1c00470
dc.identifier.issn15499596
dc.identifier.urihttps://hdl.handle.net/1843/80352
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofJournal of Chemical Information and Modeling
dc.rightsAcesso Restrito
dc.subjectBiofísica
dc.subjectÁcidos nucleicos
dc.subjectOncogenes
dc.subject.otherLocked Nucleic Acids
dc.subject.otherOncogenes
dc.titleComplete mesoscopic parameterization of single LNA modifications in DNA applied to oncogene probe design
dc.typeArtigo de periódico
local.citation.epage3624
local.citation.issue7
local.citation.spage3615
local.citation.volume61
local.description.resumoThe use of mesoscopic models to describe thethermodynamic properties of locked nucleic acid (LNA)-modifiednucleotides can provide useful insights into their properties, such ashydrogen-bonding and stacking interactions. In addition, themesoscopic parameters can be used to optimize LNA insertionin probes, to achieve accurate melting temperature predictions, andto obtain duplex opening profiles at the base-pair level. Here, weapplied this type of model to parameterize a large set of meltingtemperatures for LNA-modified sequences, from publishedsources, covering all possible nearest-neighbor configurations. Wehave found a very large increase in Morse potentials, whichindicates very strong hydrogen bonding as the main cause ofimproved LNA thermodynamic stability. LNA-modified adenine−thymine (AT) was found to have similar hydrogen bonding tounmodified cytosine−guanine (CG) base pairs, while for LNA CG, we found exceptionally large hydrogen bonding. In contrast,stacking interactions, which were thought to be behind the stability of LNA, were similar to unmodified DNA in most cases. Weapplied the new LNA parameters to the design ofBRAF,KRAS, andEGFRoncogene variants by testing all possible LNAmodifications. Selected sequences were then synthesized and had their hybridization temperatures measured, achieving a predictionaccuracy within 1°C. We performed a detailed base-pair opening analysis to discuss specific aspects of these probe hybridizationsthat may be relevant for probe design.
local.identifier.orcidhttps://orcid.org/0000-0002-5094-2595
local.identifier.orcidhttps://orcid.org/0000-0003-4878-0301
local.identifier.orcidhttps://orcid.org/0000-0002-2935-1571
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE FÍSICA
local.publisher.initialsUFMG
local.url.externahttps://pubs.acs.org/doi/10.1021/acs.jcim.1c00470

Arquivos

Licença do pacote

Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
License.txt
Tamanho:
1.99 KB
Formato:
Plain Text
Descrição:
Baixar

Coleções

Artigo de Periódico

Logo UFMG