Multivalent Interactions of Polyamide Based Sequence‐Controlled Glycomacromolecules with Concanavalin A

Binding of mannose presenting macromolecules to the protein receptor concanavalin A (ConA) is investigated by means of single‐molecule atomic force spectroscopy (SMFS) in combination with dynamic light scattering and molecular modeling. Oligomeric (Mw ≈ 1.5–2.5 kDa) and polymeric (Mw ≈ 22–30 kDa) gl...

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Bibliographic Details
Published in:	Macromolecular bioscience Vol. 19; no. 6; pp. e1900033 - n/a
Main Authors:	Camaleño de la Calle, Alberto, Gerke, Christoph, Chang, Xi Jeffrey, Grafmüller, Andrea, Hartmann, Laura, Schmidt, Stephan
Format:	Journal Article
Language:	English
Published:	Germany Wiley Subscription Services, Inc 01-06-2019
Subjects:	Atomic beam spectroscopy Binding sites Bonding strength Clustering Coiling Coils Concanavalin A Concanavalin A - chemistry Concanavalin A - ultrastructure Coupling (molecular) glycan glycocluster glycopolymer Glycopolymers Hydrogen Bonding lectin Ligands Light scattering Macromolecular Substances - chemistry Macromolecular Substances - ultrastructure Macromolecules Mannose Mannose - chemistry Molecular Conformation Molecular modelling multivalency Oligomers Photon correlation spectroscopy Polyamide resins Polyamides Polymers - chemistry Protein Binding Receptors, Concanavalin A - chemistry Receptors, Concanavalin A - ultrastructure Scaffolds signal transduction Single Molecule Imaging single‐molecule AFM Solid phase methods Solid phase synthesis Solid phases Spectrophotometry, Atomic Spectroscopy glycan glycocluster signal transduction single-molecule AFM lectin glycopolymer multivalency
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Summary:	Binding of mannose presenting macromolecules to the protein receptor concanavalin A (ConA) is investigated by means of single‐molecule atomic force spectroscopy (SMFS) in combination with dynamic light scattering and molecular modeling. Oligomeric (Mw ≈ 1.5–2.5 kDa) and polymeric (Mw ≈ 22–30 kDa) glycomacromolecules with controlled number and positioning of mannose units along the scaffolds accessible by combining solid phase synthesis and thiol–ene coupling are used as model systems to assess the molecular mechanisms that contribute to multivalent ConA–mannose complexes. SMFS measurements show increasing dissociation force from monovalent (≈57 pN) to pentavalent oligomers (≈75 pN) suggesting subsite binding to ConA. Polymeric glycomacromolecules with larger hydrodynamic diameters compared to the binding site spacing of ConA exhibit larger dissociation forces (≈80 pN), indicating simultaneous dissociation from multiple ConA binding sites. Nevertheless, although simultaneous dissociation of multiple ligands could be expected for such multivalent systems, predominantly single dissociation events are observed. This is rationalized by strong coiling of the macromolecules' polyamide backbone due to intramolecular hydrogen bonding hindering unfolding of the coil. Therefore, this study shows that the design of glycopolymers for multivalent receptor binding and clustering must consider 3D structure and intramolecular interactions of the scaffold. Specific binding of glycomacromolecules is analyzed as a function of their size and valency. Rupture force measured by AFM increases for larger mannose densities indicating multivalency by subsite binding to the lectin. Multiple unbinding events due to glycoclustering are surprisingly scarce owing to strong intermolecular interactions and coiling of the scaffolds.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1616-5187 1616-5195
DOI:	10.1002/mabi.201900033