title: Shape-persistent and adaptive multivalency: rigid transgeden (TGD) and flexible PAMAM dendrimers for heparin binding.
abstract: This study investigates transgeden (TGD) dendrimers (polyamidoamine (PAMAM)-type dendrimers modified with rigid polyphenylenevinylene (PPV) cores) and compares their heparin-binding ability with commercially available PAMAM dendrimers. Although the peripheral ligands are near-identical between the two dendrimer families, their heparin binding is very different. At low generation (G1), TGD outperforms PAMAM, but at higher generation (G2 and G3), the PAMAMs are better. Heparin binding also depends strongly on the dendrimer/heparin ratio. We explain these effects using multiscale modelling. TGD dendrimers exhibit "shape-persistent multivalency"; the rigidity means that small clusters of surface amines are locally well optimised for target binding, but it prevents the overall nanoscale structure from rearranging to maximise its contacts with a single heparin chain. Conversely, PAMAM dendrimers exhibit "adaptive multivalency"; the flexibility means individual surface ligands are not so well optimised locally to bind heparin chains, but the nanostructure can adapt more easily and maximise its binding contacts. As such, this study exemplifies important new paradigms in multivalent biomolecular recognition.
authors: Department of Chemistry, University of York, Heslington, York, YO10 5DD (UK).
authors: Stephen M
authors: SM
authors: Bromfield
authors: Paola
authors: P
authors: Posocco
authors: Maurizio
authors: M
authors: Fermeglia
authors: Juan
authors: J
authors: Tolosa
authors: Ana
authors: A
authors: Herreros-López
authors: Sabrina
authors: S
authors: Pricl
authors: Julián
authors: J
authors: Rodríguez-López
authors: David K
authors: DK
authors: Smith
mesh_terms: D050091:Dendrimers / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry
chemical_list: D050091:Dendrimers; D008024:Ligands; C104700:PAMAM Starburst; D011108:Polymers; D011145:Polyvinyls; D006493:Heparin; C041325:polyphenylene sulfide
keywords: dendrimers; heparin; molecular recognition; multiscale molecular modeling; multivalency