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Article: Evolution of abiotic cubane chemistries in a nucleic acid aptamer allows selective recognition of a malaria biomarker

TitleEvolution of abiotic cubane chemistries in a nucleic acid aptamer allows selective recognition of a malaria biomarker
Authors
Keywordsmodified aptamer
SELEX
X-ray crystallography
cubane
malaria diagnosis
Issue Date2020
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2020, v. 117 n. 29, p. 16790-16798 How to Cite?
AbstractNucleic acid aptamers selected through systematic evolution of ligands by exponential enrichment (SELEX) fold into exquisite globular structures in complex with protein targets with diverse translational applications. Varying the chemistry of nucleotides allows evolution of nonnatural nucleic acids, but the extent to which exotic chemistries can be integrated into a SELEX selection to evolve nonnatural macromolecular binding interfaces is unclear. Here, we report the identification of a cubane-modified aptamer (cubamer) against the malaria biomarker Plasmodium vivax lactate dehydrogenase (PvLDH). The crystal structure of the complex reveals an unprecedented binding mechanism involving a multicubane cluster within a hydrophobic pocket. The binding interaction is further stabilized through hydrogen bonding via cubyl hydrogens, previously unobserved in macromolecular binding interfaces. This binding mechanism allows discriminatory recognition of P. vivax over Plasmodium falciparum lactate dehydrogenase, thereby distinguishing these highly conserved malaria biomarkers for diagnostic applications. Together, our data demonstrate that SELEX can be used to evolve exotic nucleic acids bearing chemical functional groups which enable remarkable binding mechanisms which have never been observed in biology. Extending to other exotic chemistries will open a myriad of possibilities for functional nucleic acids.
Persistent Identifierhttp://hdl.handle.net/10722/290056
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, YW-
dc.contributor.authorRöthlisberger, P-
dc.contributor.authorMechaly, AE-
dc.contributor.authorWeber, P-
dc.contributor.authorLevi-Acobas, F-
dc.contributor.authorLO, Y-
dc.contributor.authorWONG, AWC-
dc.contributor.authorKinghorn, AB-
dc.contributor.authorHaouz, A-
dc.contributor.authorSavage, GP-
dc.contributor.authorHollenstein, M-
dc.contributor.authorTanner, JA-
dc.date.accessioned2020-10-22T08:21:28Z-
dc.date.available2020-10-22T08:21:28Z-
dc.date.issued2020-
dc.identifier.citationProceedings of the National Academy of Sciences, 2020, v. 117 n. 29, p. 16790-16798-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/290056-
dc.description.abstractNucleic acid aptamers selected through systematic evolution of ligands by exponential enrichment (SELEX) fold into exquisite globular structures in complex with protein targets with diverse translational applications. Varying the chemistry of nucleotides allows evolution of nonnatural nucleic acids, but the extent to which exotic chemistries can be integrated into a SELEX selection to evolve nonnatural macromolecular binding interfaces is unclear. Here, we report the identification of a cubane-modified aptamer (cubamer) against the malaria biomarker Plasmodium vivax lactate dehydrogenase (PvLDH). The crystal structure of the complex reveals an unprecedented binding mechanism involving a multicubane cluster within a hydrophobic pocket. The binding interaction is further stabilized through hydrogen bonding via cubyl hydrogens, previously unobserved in macromolecular binding interfaces. This binding mechanism allows discriminatory recognition of P. vivax over Plasmodium falciparum lactate dehydrogenase, thereby distinguishing these highly conserved malaria biomarkers for diagnostic applications. Together, our data demonstrate that SELEX can be used to evolve exotic nucleic acids bearing chemical functional groups which enable remarkable binding mechanisms which have never been observed in biology. Extending to other exotic chemistries will open a myriad of possibilities for functional nucleic acids.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subjectmodified aptamer-
dc.subjectSELEX-
dc.subjectX-ray crystallography-
dc.subjectcubane-
dc.subjectmalaria diagnosis-
dc.titleEvolution of abiotic cubane chemistries in a nucleic acid aptamer allows selective recognition of a malaria biomarker-
dc.typeArticle-
dc.identifier.emailKinghorn, AB: kinghorn@hku.hk-
dc.identifier.emailTanner, JA: jatanner@hkucc.hku.hk-
dc.identifier.authorityTanner, JA=rp00495-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.2003267117-
dc.identifier.pmid32631977-
dc.identifier.pmcidPMC7382308-
dc.identifier.scopuseid_2-s2.0-85088881499-
dc.identifier.hkuros316967-
dc.identifier.volume117-
dc.identifier.issue29-
dc.identifier.spage16790-
dc.identifier.epage16798-
dc.identifier.isiWOS:000557946500017-
dc.publisher.placeUnited States-
dc.identifier.issnl0027-8424-

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