title: Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent Protein-Ligand Interactions.
abstract: A highly efficient cap-exchange approach for preparing compact, dense polyvalent mannose-capped quantum dots (QDs) has been developed. The resulting QDs have been successfully used to probe multivalent interactions of HIV/Ebola receptors DC-SIGN and DC-SIGNR (collectively termed as DC-SIGN/R) using a sensitive, ratiometric Förster resonance energy transfer (FRET) assay. The QD probes specifically bind DC-SIGN, but not its closely related receptor DC-SIGNR, which is further confirmed by its specific blocking of DC-SIGN engagement with the Ebola virus glycoprotein. Tuning the QD surface mannose valency reveals that DC-SIGN binds more efficiently to densely packed mannosides. A FRET-based thermodynamic study reveals that the binding is enthalpy-driven. This work establishes QD FRET as a rapid, sensitive technique for probing structure and thermodynamics of multivalent protein-ligand interactions.
authors.affiliation: School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. y.guo@leeds.ac.uk.
authors.forename: Yuan
authors.identifier: http://orcid.org/0000-0003-4607-7356
authors.initials: Y
authors.lastname: Guo
authors.affiliation: School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Chadamas
authors.initials: C
authors.lastname: Sakonsinsiri
authors.affiliation: Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Nehlmeier
authors.affiliation: Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Fascione
authors.affiliation: School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Weili
authors.initials: W
authors.lastname: Wang
authors.affiliation: Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
authors.affiliation: School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: W Bruce
authors.identifier: http://orcid.org/0000-0002-7352-0360
authors.initials: WB
authors.lastname: Turnbull
authors.affiliation: School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. d.zhou@leeds.ac.uk.
authors.forename: Dejian
authors.identifier: http://orcid.org/0000-0003-3314-9242
authors.initials: D
authors.lastname: Zhou
mesh_terms: D015815:Cell Adhesion Molecules / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D037181:Lectins, C-Type / Q000737:chemistry; D008024:Ligands; D008358:Mannose / Q000737:chemistry*; D015335:Molecular Probes / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D045663:Quantum Dots; D011956:Receptors, Cell Surface / Q000737:chemistry; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008024:Ligands; D008358:Mannose; D015335:Molecular Probes; D011506:Proteins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: FRET; carbohydrates; proteins; quantum dots; viral inhibition