학술논문
Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif.
Document Type
Academic Journal
Author
Schofield P; Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Kensington, Sydney, NSW 2010, Australia.; Taylor AI; MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, UK.; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), University of Cambridge, Cambridge CB2 0AW, UK.; Rihon J; Rega Institute, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Herestraat 49, B 3000, Leuven, Belgium.; Peña Martinez CD; Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Kensington, Sydney, NSW 2010, Australia.; Zinn S; Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Kensington, Sydney, NSW 2010, Australia.; Mattelaer CA; Rega Institute, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Herestraat 49, B 3000, Leuven, Belgium.; Jackson J; Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.; Dhaliwal G; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), University of Cambridge, Cambridge CB2 0AW, UK.; Schepers G; Rega Institute, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Herestraat 49, B 3000, Leuven, Belgium.; Herdewijn P; Rega Institute, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Herestraat 49, B 3000, Leuven, Belgium.; Lescrinier E; Rega Institute, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Herestraat 49, B 3000, Leuven, Belgium.; Christ D; Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Kensington, Sydney, NSW 2010, Australia.; Holliger P; MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, UK.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
Subject
Language
English
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.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
(© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)