Synthesis of All Possible Canonical (3'-5'-Linked) Cyclic Dinucleotides and Evaluation of Riboswitch Interactions and Immune-Stimulatory Effects

Wang, Changhao; Sinn, Malte; Stifel, Julia; Heiler, Anna Carola; Sommershof, Annette; Hartig, Jörg S.

Synthesis of All Possible Canonical (3'-5'-Linked) Cyclic Dinucleotides and Evaluation of Riboswitch Interactions and Immune-Stimulatory Effects

Dateien

Wang_2-56wcq6vnhmmp4.pdfGröße: 353.11 KBDownloads: 720

Datum

2017

Angaben zur Forschungsförderung

European Union (EU): 681777

Projekt

RiboDisc

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Chemie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Journal of the American Chemical Society. 2017, 139(45), pp. 16154-16160. ISSN 0002-7863. eISSN 1520-5126. Available under: doi: 10.1021/jacs.7b06141

Zusammenfassung

The cyclic dinucleotides (CDNs) c-di-GMP, c-di-AMP, and c-AMP-GMP are widely utilized as second messengers in bacteria, where they signal lifestyle changes such as motility and biofilm formation, cell wall and membrane homeostasis, virulence, and exo-electrogenesis. For all known bacterial CDNs, specific riboswitches have been identified that alter gene expression in response to the second messengers. In addition, bacterial CDNs trigger potent immune responses, making them attractive as adjuvants in immune therapies. Besides the three naturally occurring CDNs, seven further CDNs containing canonical 3'-5'-linkages are possible by combining the four natural ribonucleotides. Herein, we have synthesized all ten possible combinations of 3'-5'-linked CDNs. The binding affinity of novel CDNs and GEMM riboswitch variants was assessed utilizing a spinach aptamer fluorescence assay and in-line probing assays. The immune-stimulatory effect of CDNs was evaluated by induction of type I interferons (IFNs), and a novel CDN c-AMP-CMP was identified as a new immune-stimulatory agent.

Fachgebiet (DDC)

540 Chemie

Zitieren

ISO 690

WANG, Changhao, Malte SINN, Julia STIFEL, Anna Carola HEILER, Annette SOMMERSHOF, Jörg S. HARTIG, 2017. Synthesis of All Possible Canonical (3'-5'-Linked) Cyclic Dinucleotides and Evaluation of Riboswitch Interactions and Immune-Stimulatory Effects. In: Journal of the American Chemical Society. 2017, 139(45), pp. 16154-16160. ISSN 0002-7863. eISSN 1520-5126. Available under: doi: 10.1021/jacs.7b06141

BibTex

@article{Wang2017-11-15Synth-40581,
  year={2017},
  doi={10.1021/jacs.7b06141},
  title={Synthesis of All Possible Canonical (3'-5'-Linked) Cyclic Dinucleotides and Evaluation of Riboswitch Interactions and Immune-Stimulatory Effects},
  number={45},
  volume={139},
  issn={0002-7863},
  journal={Journal of the American Chemical Society},
  pages={16154--16160},
  author={Wang, Changhao and Sinn, Malte and Stifel, Julia and Heiler, Anna Carola and Sommershof, Annette and Hartig, Jörg S.}
}

RDF

<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/40581">
    <dc:creator>Heiler, Anna Carola</dc:creator>
    <dcterms:abstract xml:lang="eng">The cyclic dinucleotides (CDNs) c-di-GMP, c-di-AMP, and c-AMP-GMP are widely utilized as second messengers in bacteria, where they signal lifestyle changes such as motility and biofilm formation, cell wall and membrane homeostasis, virulence, and exo-electrogenesis. For all known bacterial CDNs, specific riboswitches have been identified that alter gene expression in response to the second messengers. In addition, bacterial CDNs trigger potent immune responses, making them attractive as adjuvants in immune therapies. Besides the three naturally occurring CDNs, seven further CDNs containing canonical 3'-5'-linkages are possible by combining the four natural ribonucleotides. Herein, we have synthesized all ten possible combinations of 3'-5'-linked CDNs. The binding affinity of novel CDNs and GEMM riboswitch variants was assessed utilizing a spinach aptamer fluorescence assay and in-line probing assays. The immune-stimulatory effect of CDNs was evaluated by induction of type I interferons (IFNs), and a novel CDN c-AMP-CMP was identified as a new immune-stimulatory agent.</dcterms:abstract>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:language>eng</dc:language>
    <dc:contributor>Wang, Changhao</dc:contributor>
    <dc:creator>Sinn, Malte</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Wang, Changhao</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-11-10T13:57:39Z</dc:date>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-11-10T13:57:39Z</dcterms:available>
    <dc:contributor>Sinn, Malte</dc:contributor>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:creator>Sommershof, Annette</dc:creator>
    <dc:contributor>Stifel, Julia</dc:contributor>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/40581/1/Wang_2-56wcq6vnhmmp4.pdf"/>
    <dc:contributor>Sommershof, Annette</dc:contributor>
    <dc:contributor>Heiler, Anna Carola</dc:contributor>
    <dc:creator>Stifel, Julia</dc:creator>
    <dcterms:title>Synthesis of All Possible Canonical (3'-5'-Linked) Cyclic Dinucleotides and Evaluation of Riboswitch Interactions and Immune-Stimulatory Effects</dcterms:title>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:contributor>Hartig, Jörg S.</dc:contributor>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/40581"/>
    <dc:creator>Hartig, Jörg S.</dc:creator>
    <dc:rights>terms-of-use</dc:rights>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/40581/1/Wang_2-56wcq6vnhmmp4.pdf"/>
    <dcterms:issued>2017-11-15</dcterms:issued>
  </rdf:Description>
</rdf:RDF>

Universitätsbibliographie

Ja