title: Protein-triggered supramolecular disassembly: insights based on variations in ligand location in amphiphilic dendrons.
abstract: We use monodisperse dendrons that allow control over functional group presentation to investigate the influence of the location of a ligand on protein-induced disassembly and release of encapsulated small molecules. Based on both experiments and molecular dynamics simulations, we demonstrate that ligand location greatly influences release of guest molecules from the dendron-based supramolecular assembly. We show that a ligand moiety grafted to the dendron periphery is more accessible for the target protein in aqueous solution. On the other hand, the ligand moiety placed at the focal point or at the intermediate layer within the dendritic scaffold is less accessible, since it is surrounded by an environment rich in PEG chains, which hinders binding and even influences nonspecific interactions. We also demonstrate that the specific binding between one ligand and the target protein can destabilize the dendritic assembly. Furthermore, if more ligands are available, multivalent interactions are also possible with extravidin, which speed up disassembly and trigger the release of hydrophobic guests.
authors.affiliation: Department of Chemistry, University of Massachusetts , Amherst, Massachusetts 01003, United States.
authors.forename: Diego
authors.initials: D
authors.lastname: Amado Torres
authors.forename: Matteo
authors.initials: M
authors.lastname: Garzoni
authors.forename: Ayyagari V
authors.initials: AV
authors.lastname: Subrahmanyam
authors.forename: Giovanni M
authors.initials: GM
authors.lastname: Pavan
authors.forename: S
authors.initials: S
authors.lastname: Thayumanavan
mesh_terms: D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011506:Proteins / Q000737:chemistry*; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D008024:Ligands; D046911:Macromolecular Substances; D011506:Proteins; D013501:Surface-Active Agents