Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif. Schofield, P., Taylor, A. I, Rihon, J., Peña Martinez, C. D, Zinn, S., Mattelaer, C., Jackson, J., Dhaliwal, G., Schepers, G., Herdewijn, P., Lescrinier, E., Christ, D., & Holliger, P. Nucleic Acids Research, July, 2023. ![Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Abstract 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.
@article{schofield_characterization_2023,
title = {Characterization of an {HNA} aptamer suggests a non-canonical {G}-quadruplex motif},
issn = {0305-1048, 1362-4962},
url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad592/7223585},
doi = {10.1093/nar/gkad592},
abstract = {Abstract
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.},
language = {en},
urldate = {2023-07-27},
journal = {Nucleic Acids Research},
author = {Schofield, Peter and Taylor, Alexander I and Rihon, Jérôme and Peña Martinez, Cristian D and Zinn, Sacha and Mattelaer, Charles-Alexandre and Jackson, Jennifer and Dhaliwal, Gurpreet and Schepers, Guy and Herdewijn, Piet and Lescrinier, Eveline and Christ, Daniel and Holliger, Philipp},
month = jul,
year = {2023},
pages = {gkad592},
}
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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.","language":"en","urldate":"2023-07-27","journal":"Nucleic Acids Research","author":[{"propositions":[],"lastnames":["Schofield"],"firstnames":["Peter"],"suffixes":[]},{"propositions":[],"lastnames":["Taylor"],"firstnames":["Alexander","I"],"suffixes":[]},{"propositions":[],"lastnames":["Rihon"],"firstnames":["Jérôme"],"suffixes":[]},{"propositions":[],"lastnames":["Peña Martinez"],"firstnames":["Cristian","D"],"suffixes":[]},{"propositions":[],"lastnames":["Zinn"],"firstnames":["Sacha"],"suffixes":[]},{"propositions":[],"lastnames":["Mattelaer"],"firstnames":["Charles-Alexandre"],"suffixes":[]},{"propositions":[],"lastnames":["Jackson"],"firstnames":["Jennifer"],"suffixes":[]},{"propositions":[],"lastnames":["Dhaliwal"],"firstnames":["Gurpreet"],"suffixes":[]},{"propositions":[],"lastnames":["Schepers"],"firstnames":["Guy"],"suffixes":[]},{"propositions":[],"lastnames":["Herdewijn"],"firstnames":["Piet"],"suffixes":[]},{"propositions":[],"lastnames":["Lescrinier"],"firstnames":["Eveline"],"suffixes":[]},{"propositions":[],"lastnames":["Christ"],"firstnames":["Daniel"],"suffixes":[]},{"propositions":[],"lastnames":["Holliger"],"firstnames":["Philipp"],"suffixes":[]}],"month":"July","year":"2023","pages":"gkad592","bibtex":"@article{schofield_characterization_2023,\n\ttitle = {Characterization of an {HNA} aptamer suggests a non-canonical {G}-quadruplex motif},\n\tissn = {0305-1048, 1362-4962},\n\turl = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad592/7223585},\n\tdoi = {10.1093/nar/gkad592},\n\tabstract = {Abstract\n 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. 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