Journal article
Dendrimers destabilize proteins in a generation-dependent manner involving electrostatic interactions
Innate Immunology, Division of Veterinary Diagnostics and Research, National Veterinary Institute, Technical University of Denmark1
Division of Veterinary Diagnostics and Research, National Veterinary Institute, Technical University of Denmark2
National Veterinary Institute, Technical University of Denmark3
Dendrimers are well-defined chemical polymers with a characteristic branching pattern that gives rise to attractive features such as antibacterial and antitumor activities as well as drug delivery properties. In addition, dendrimers can solubilize prion protein aggregates at very low concentrations, but their mode of action is unclear.
We show that poly(propylene imine) dendrimers based on di-aminobutane (DAB) and modified with guanidinium surface groups reduce insulin thermostability and solubility considerably at microgram per microliter concentrations, while urea-modified groups have hardly any effect. Destabilization is markedly generation-dependent and is most pronounced for generation 3, which is also the most efficient at precipitating insulin.
This suggests that proteins can interact with both dendrimer sui-face and interior. The pH-dependence reveals that interactions are mainly mediated by electrostatics, confirmed by studies on four other proteins. Ability to precipitate and destabilize are positively correlated, in contrast to conventional small-molecule denaturants and stabilizers, indicating that surface immobilization of denaturing groups profoundly affects its interactions with proteins.
Language: | English |
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Publisher: | Wiley Subscription Services, Inc., A Wiley Company |
Year: | 2008 |
Pages: | 522-529 |
ISSN: | 10970282 and 00063525 |
Types: | Journal article |
DOI: | 10.1002/bip.20921 |
ORCIDs: | Heegaard, Peter M. H. |