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Dendrimers destabilize proteins in a generation‐dependent manner involving electrostatic interactions
Author(s) -
Giehm Lise,
Christensen Casper,
Boas Ulrik,
Heegaard Peter M. H.,
Otzen Daniel E.
Publication year - 2008
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20921
Subject(s) - dendrimer , chemistry , thermostability , solubility , polymer , biophysics , combinatorial chemistry , chemical engineering , organic chemistry , engineering , biology , enzyme
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. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 522–529, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com