Dendrimer–protein interactions studied by tryptophan room temperature phosphorescence

Gabellieri, Edi; Strambini, Giovanni B.; Shcharbin, Dzmitry; Klajnert, Barbara; Bryszewska, Maria

doi:10.1016/j.bbapap.2006.09.008

Cited by 38 publications

(48 citation statements)

References 32 publications

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“…[44] Similarly, anionic patches on the otherwise positively charged surface of lactate dehydrogenase (LADH) were invoked to explain why cationic PAMAM G5 loses its affinity for LADH in the presence of NaCl. [39] Continuing this theme, Tsukube and coworkers constructed an elegantly focused ''patch-dendrimer'' [40] by combining hydrophobic benzylether dendron elements with polyanionic heptaglutamic acid to target the polycationic patch on cytochrome c. This succeeded very well, since G3-G5 dendrimers all showed 30-to 500-fold greater affinity for cytochrome c than did the protein's natural ligand, cytochrome b 5 . Interestingly, however, the affinity for cytochrome c decreased with higher generations, possibly because the growing size of the hydrophobic dendron units blocks access to the negative heptaglutamic acid patch.…”

Section: The General Interaction Of Dendrimers With Proteinmentioning

confidence: 81%

“…[39] Nevertheless, binding is surprisingly specific, with affinities in the low micro molar region and stoichiometries around 1:1, although this depends on the size of the dendrimer. [39,40] In addition to these general features, there will of course be the possibility of specific proteinligand interactions as seen for folate-derivatized PAMAM dendrimers and folate-binding protein, [41] and interactions between Ab peptide and sialic acid-conjugated dendrimers. [42] These can, for sialic acid-displaying G5 dendrimers, lead to K d values as low as 10 Â 10 À9 M, [42] which is several orders of magnitude higher than the affinity of Ab for naturally occurring sialic acid-containing gangliosides on the cell membrane due to the dendritic effect (see above).…”

Section: The General Interaction Of Dendrimers With Proteinmentioning

confidence: 99%

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Dendrimer Effects on Peptide and Protein Fibrillation

Heegaard

Boas

Otzen

2007

Macromolecular Bioscience

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Dendrimers are synthetic, symmetrically branched polymers that can be manufactured to a high degree of definition and therefore present themselves as monodisperse entities. Flexible and globular in shape and compartementalized into a partly inaccessible interior and a highly exposed surface, they offer numerous possibilities for interactions with and responses to biological macromolecules and biostructures including cell membranes and proteins. By way of their multiple functional surface groups, they allow the design of surfaces carrying a multitude of biological motifs and/or charges giving rise to quite significant biological and physico-chemical effects. Here we describe the surprising ability of dendrimers to interact with and perturb polypeptide conformations, particularly efficiently towards amyloid structures; that is, the structures of highly insoluble polypeptide aggregates involved in a range of serious and irreversibly progressive pathological conditions (protein-misfolding diseases). Interesting as this may be, the interaction of dendrimers with such generic peptidic aggregates also offers a new perspective on the molecular mechanisms governing assembly and disassembly of amyloid structures and thereby on determinants of protein and peptide folding. Despite the potent disaggregative nature of various dendrimers, they have variable effects on the stability of different proteins, suggesting that they do not act as generic denaturants, but rather exert their effects via specific interactions with individual parts of each protein.

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Section: The General Interaction Of Dendrimers With Proteinmentioning

confidence: 81%

Section: The General Interaction Of Dendrimers With Proteinmentioning

confidence: 99%

Dendrimer Effects on Peptide and Protein Fibrillation

Heegaard

Boas

Otzen

2007

Macromolecular Bioscience

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“…15,32 This will make it difficult in general to predict whether a given protein will be destabilized or unaffected by dendrimers. However, our data show that overall charge can provide useful starting information.…”

Section: Dendrimers Affect Protein Stability Mainly By Electrostatic mentioning

confidence: 99%

“…Thus, a very recent phosphorescence study reported structural changed in flexible regions of the polypeptide. 15 Increasing concentrations of PAMAM dendrimers destabilize bovine serum albumin 16 but slightly increase the thermal stability of human serum albumin. 17 To provide more insights into these apparently contradictory observations, we here describe interactions between insulin and different modifications of a PPI-type dendrimer based on di-aminobutane (DAB).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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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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“…Protein RTTP lifetimes depend strongly on oxygen removal [17][18][19][20][21][22]. The strong interaction of dendrimers with a protein surface can restrict the effective removal of oxygen from a protein globule [17][18][19][20][21][22], which results in a significant decrease of RTTP. As follows from data on zetapotentials, dendrimers have the strongest interaction with AP (Fig.…”

Section: Resultsmentioning

confidence: 99%