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Shape‐Persistent and Adaptive Multivalency: Rigid Transgeden (TGD) and Flexible PAMAM Dendrimers for Heparin Binding
Author(s) -
Bromfield Stephen M.,
Posocco Paola,
Fermeglia Maurizio,
Tolosa Juan,
HerrerosLópez Ana,
Pricl Sabrina,
RodríguezLópez Julián,
Smith David K.
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201402237
Subject(s) - dendrimer , heparin , chemistry , rigidity (electromagnetism) , structural rigidity , nanostructure , nanoscopic scale , polymer , nanotechnology , biophysics , flexibility (engineering) , materials science , chemical physics , polymer chemistry , organic chemistry , mathematics , biochemistry , composite material , biology , geometry , statistics
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.