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2020-08-04Zeitschriftenartikel DOI: 10.18452/22169
Rational Design of a DNA-Scaffolded High-Affinity Binder for Langerin
dc.contributor.authorBachem, Gunnar
dc.contributor.authorWamhoff, Eike-Christian
dc.contributor.authorSilberreis, Kim
dc.contributor.authorKim, Dongyoon
dc.contributor.authorBaukmann, Hannes
dc.contributor.authorFuchsberger, Felix F.
dc.contributor.authorDernedde, Jens
dc.contributor.authorRademacher, Christoph
dc.contributor.authorSeitz, Oliver
dc.contributor.authorFuchsberger, Felix
dc.date.accessioned2020-11-19T11:24:25Z
dc.date.available2020-11-19T11:24:25Z
dc.date.issued2020-08-04none
dc.identifier.other10.1002/anie.202006880
dc.identifier.urihttp://edoc.hu-berlin.de/18452/22794
dc.description.abstractBinders of langerin could target vaccines to Langerhans cells for improved therapeutic effect. Since langerin has low affinity for monovalent glycan ligands, highly multivalent presentation has previously been key for targeting. Aiming to reduce the amount of ligand required, we rationally designed molecularly defined high‐affinity binders based on the precise display of glycomimetic ligands (Glc2NTs) on DNA‐PNA scaffolds. Rather than mimicking langerin's homotrimeric structure with a C3‐symmetric scaffold, we developed readily accessible, easy‐to‐design bivalent binders. The method considers the requirements for bridging sugar binding sites and statistical rebinding as a means to both strengthen the interactions at single binding sites and amplify the avidity enhancement provided by chelation. This gave a 1150‐fold net improvement over the affinity of the free ligand and provided a nanomolar binder (IC50=300 nM) for specific internalization by langerin‐expressing cells.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectcarbohydrate recognitioneng
dc.subjectDNA nanotechnologyeng
dc.subjectlectinseng
dc.subjectmultivalent interactionseng
dc.subjectpeptide nucleic acidseng
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftennone
dc.titleRational Design of a DNA-Scaffolded High-Affinity Binder for Langerinnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/22794-9
dc.identifier.doihttp://dx.doi.org/10.18452/22169
dc.type.versionpublishedVersionnone
local.edoc.container-titleAngewandte Chemienone
local.edoc.type-nameZeitschriftenartikel
local.edoc.institutionMathematisch-Naturwissenschaftliche Fakultätnone
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-publisher-nameWiley-VCHnone
local.edoc.container-publisher-placeWeinheimnone
local.edoc.container-volume59none
local.edoc.container-issue47none
local.edoc.container-firstpage21016none
local.edoc.container-lastpage21022none
dc.description.versionPeer Reviewednone
dc.identifier.eissn1521-3773

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