Aufgrund von Vorbereitungen auf eine neue Version von KOPS, können kommenden Montag und Dienstag keine Publikationen eingereicht werden. (Due to preparations for a new version of KOPS, no publications can be submitted next Monday and Tuesday.)

Structural Basis of Multivalent Binding to Wheat Germ Agglutinin

Cite This

Files in this item

Checksum: MD5:95c75fcdb663cecef8c657320ed1d919

SCHWEFEL, David, Caroline MAIERHOFER, Johannes G. BECK, Sonja SEEBERGER, Kay DIEDERICHS, Heiko MÖLLER, Wolfram WELTE, Valentin WITTMANN, 2010. Structural Basis of Multivalent Binding to Wheat Germ Agglutinin. In: Journal of the American Chemical Society. 132(25), pp. 8704-8719. ISSN 0002-7863. eISSN 1520-5126. Available under: doi: 10.1021/ja101646k

@article{Schwefel2010Struc-13611, title={Structural Basis of Multivalent Binding to Wheat Germ Agglutinin}, year={2010}, doi={10.1021/ja101646k}, number={25}, volume={132}, issn={0002-7863}, journal={Journal of the American Chemical Society}, pages={8704--8719}, author={Schwefel, David and Maierhofer, Caroline and Beck, Johannes G. and Seeberger, Sonja and Diederichs, Kay and Möller, Heiko and Welte, Wolfram and Wittmann, Valentin} }

<rdf:RDF xmlns:dcterms="" xmlns:dc="" xmlns:rdf="" xmlns:bibo="" xmlns:dspace="" xmlns:foaf="" xmlns:void="" xmlns:xsd="" > <rdf:Description rdf:about=""> <dc:contributor>Möller, Heiko</dc:contributor> <dc:contributor>Schwefel, David</dc:contributor> <dc:creator>Beck, Johannes G.</dc:creator> <dcterms:isPartOf rdf:resource=""/> <dcterms:available rdf:datatype="">2011-06-09T07:17:38Z</dcterms:available> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dspace:isPartOfCollection rdf:resource=""/> <dc:creator>Seeberger, Sonja</dc:creator> <dc:contributor>Wittmann, Valentin</dc:contributor> <bibo:uri rdf:resource=""/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:creator>Diederichs, Kay</dc:creator> <dc:rights>terms-of-use</dc:rights> <dc:creator>Wittmann, Valentin</dc:creator> <dc:language>eng</dc:language> <dcterms:title>Structural Basis of Multivalent Binding to Wheat Germ Agglutinin</dcterms:title> <dc:creator>Möller, Heiko</dc:creator> <dc:contributor>Welte, Wolfram</dc:contributor> <dcterms:issued>2010</dcterms:issued> <dcterms:hasPart rdf:resource=""/> <dcterms:rights rdf:resource=""/> <dc:contributor>Maierhofer, Caroline</dc:contributor> <dc:contributor>Seeberger, Sonja</dc:contributor> <dc:creator>Welte, Wolfram</dc:creator> <dc:creator>Maierhofer, Caroline</dc:creator> <dc:date rdf:datatype="">2011-06-09T07:17:38Z</dc:date> <dc:contributor>Diederichs, Kay</dc:contributor> <dcterms:bibliographicCitation>First publ. in: Journal of the American Chemical Society 132 (2010), 25, pp. 8704-8719, DOI: 10.1021/ja101646k</dcterms:bibliographicCitation> <dcterms:abstract xml:lang="eng">The inhibition of carbohydrate−protein interactions by tailored multivalent ligands is a powerful strategy for the treatment of many human diseases. Crucial for the success of this approach is an understanding of the molecular mechanisms as to how a binding enhancement of a multivalent ligand is achieved. We have synthesized a series of multivalent N-acetylglucosamine (GlcNAc) derivatives and studied their interaction with the plant lectin wheat germ agglutinin (WGA) by an enzyme-linked lectin assay (ELLA) and X-ray crystallography. The solution conformation of one ligand was determined by NMR spectroscopy. Employing a GlcNAc carbamate motif with α-configuration and by systematic variation of the spacer length, we were able to identify divalent ligands with unprecedented high WGA binding potency. The best divalent ligand has an IC50 value of 9.8 μM (ELLA) corresponding to a relative potency of 2350 (1170 on a valency-corrected basis, i.e., per mol sugar contained) compared to free GlcNAc. X-ray crystallography of the complex of WGA and the second best, closely related divalent ligand explains this activity. Four divalent molecules simultaneously bind to WGA with each ligand bridging adjacent binding sites. This shows for the first time that all eight sugar binding sites of the WGA dimer are simultaneously functional. We also report a tetravalent neoglycopeptide with an IC50 value of 0.9 μM being 25500 times higher than that of GlcNAc (6400 times per contained sugar) and the X-ray structure analysis of its complex with glutaraldehyde-cross-linked WGA. Comparison of the crystal structure and the solution NMR structure of the neoglycopeptide as well as results from the ELLA suggest that the conformation of the glycopeptide in solution is already preorganized in a way supporting multivalent binding to the protein. Our findings show that bridging adjacent protein binding sites by multivalent ligands is a valid strategy to find high-affinity protein ligands and that even subtle changes of the linker structure can have a significant impact on the binding affinity.</dcterms:abstract> <dc:contributor>Beck, Johannes G.</dc:contributor> <dc:creator>Schwefel, David</dc:creator> <dspace:hasBitstream rdf:resource=""/> </rdf:Description> </rdf:RDF>

Downloads since Oct 1, 2014 (Information about access statistics)

schwefel_jacs_2010.pdf 1339

This item appears in the following Collection(s)

Search KOPS


My Account