Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
25 08 2023
25 08 2023
Historique:
accepted:
05
07
2023
revised:
09
06
2023
received:
16
03
2021
medline:
28
8
2023
pubmed:
13
7
2023
entrez:
13
7
2023
Statut:
ppublish
Résumé
Nucleic acids not only form the basis of heredity, but are increasingly a source of novel nano-structures, -devices and drugs. This has spurred the development of chemically modified alternatives (xeno nucleic acids (XNAs)) comprising chemical configurations not found in nature to extend their chemical and functional scope. XNAs can be evolved into ligands (XNA aptamers) that bind their targets with high affinity and specificity. However, detailed investigations into structural and functional aspects of XNA aptamers have been limited. Here we describe a detailed structure-function analysis of LYS-S8-19, a 1',5'-anhydrohexitol nucleic acid (HNA) aptamer to hen egg-white lysozyme (HEL). Mapping of the aptamer interaction interface with its cognate HEL target antigen revealed interaction epitopes, affinities, kinetics and hot-spots of binding energy similar to protein ligands such as anti-HEL-nanobodies. Truncation analysis and molecular dynamics (MD) simulations suggest that the HNA aptamer core motif folds into a novel and not previously observed HNA tertiary structure, comprising non-canonical hT-hA-hT/hT-hT-hT triplet and hG4-quadruplex structures, consistent with its recognition by two different G4-specific antibodies.
Identifiants
pubmed: 37439359
pii: 7223585
doi: 10.1093/nar/gkad592
pmc: PMC10450178
doi:
Substances chimiques
Ligands
0
Aptamers, Nucleotide
0
Nucleic Acids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7736-7748Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : 09-EuroSYNBIO-OP-013/INTENSIFY
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105178804
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 215453/Z/19/Z
Pays : United Kingdom
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
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