Dendrimers destabilize proteins in a generation-dependent manner involving electrostatic interactions

Biopolymers
Lise GiehmDaniel E Otzen

Abstract

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 surface 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.

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Citations

Oct 8, 2015·Macromolecular Bioscience·Svetlana A SorokinaVladimir I Muronetz
Feb 24, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zonghua LiuWei Xue
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Nov 26, 2015·International Journal of Biological Macromolecules·Olga NowackaMaria Bryszewska
Jun 1, 2013·Advanced Materials·Min ZhangChen Wang
Feb 28, 2014·Colloids and Surfaces. B, Biointerfaces·Olga NowackaMaria Bryszewska
Nov 2, 2012·Chemical Society Reviews·Wen-de Tian, Yu-qiang Ma
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Aug 10, 2010·Biomacromolecules·Rosa DoménechJosé L Neira

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