Complexes between cationic pyridylphenylene dendrimers and ovine prion protein: do hydrophobic interactions matter?

Сорокина, С. А.; Semenyuk, Pavel I.; Stroylova, y.; Muronetz, Vladimir I.; Shifrina, Zinaida B.

doi:10.1039/c6ra26563d

Cited by 20 publications

(9 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next, we should mention modeling of the cationic or anionic dendrimers, which are extensively studied as multi-functional drug carriers [ 56 , 57 ] in complexes with different proteins: immunoglobulins [ 58 ], amyloidogenic prion protein [ 59 ], actin [ 60 ], human serum albumin [ 61 ], HIV-derived peptides [ 62 , 63 ], ferritin [ 64 ], and other proteins [ 65 ]. Interestingly, control of protonation state (and therefore the net charge) of polyamidoamine (PAMAM) dendrimers allowed control of their interaction with cytolysin A, a protein toxin forming pores in cell membrane and thus causing membrane permeabilization [ 66 ].…”

Section: Protein Interaction With Model Polymers and Nucleic Acidsmentioning

confidence: 99%

“…The first lesson learned from the study of such model systems is a deep understanding of patch-based interaction of similarly charged macromolecules. Indeed, proteins have both negatively and positively charged patches on the surface in a wide pH range, which can interact with oppositely charged regions of the polymers even if total charges of the protein and the polymer are the same [ 39 , 59 , 67 ]. The patch-based interaction model helped us to explain the chaperone-like activity of synthetic polyelectrolytes [ 68 , 69 , 70 , 71 ], which can be higher in the case of similarly charged proteins and polyelectrolytes [ 67 ].…”

Section: Protein Interaction With Model Polymers and Nucleic Acidsmentioning

confidence: 99%

See 1 more Smart Citation

Protein Interaction with Charged Macromolecules: From Model Polymers to Unfolded Proteins and Post-Translational Modifications

Semenyuk

Muronetz

2019

IJMS

View full text Add to dashboard Cite

Interaction of proteins with charged macromolecules is involved in many processes in cells. Firstly, there are many naturally occurred charged polymers such as DNA and RNA, polyphosphates, sulfated glycosaminoglycans, etc., as well as pronouncedly charged proteins such as histones or actin. Electrostatic interactions are also important for “generic” proteins, which are not generally considered as polyanions or polycations. Finally, protein behavior can be altered due to post-translational modifications such as phosphorylation, sulfation, and glycation, which change a local charge of the protein region. Herein we review molecular modeling for the investigation of such interactions, from model polyanions and polycations to unfolded proteins. We will show that electrostatic interactions are ubiquitous, and molecular dynamics simulations provide an outstanding opportunity to look inside binding and reveal the contribution of electrostatic interactions. Since a molecular dynamics simulation is only a model, we will comprehensively consider its relationship with the experimental data.

show abstract

Section: Protein Interaction With Model Polymers and Nucleic Acidsmentioning

confidence: 99%

Section: Protein Interaction With Model Polymers and Nucleic Acidsmentioning

confidence: 99%

Protein Interaction with Charged Macromolecules: From Model Polymers to Unfolded Proteins and Post-Translational Modifications

Semenyuk

Muronetz

2019

IJMS

View full text Add to dashboard Cite

show abstract

“…The results of the inhibition of amyloid aggregation by synthetic polymers have also been described. For example, cationic pyridylphenylene [38,39] and polyamidoamine [40] dendrimers exhibited anti-amyloid activity. Heparin was shown to modulate the aggregation of amyloid-beta peptide [41].…”

Section: Introductionmentioning

confidence: 99%

Alpha-Synuclein Amyloid Aggregation Is Inhibited by Sulfated Aromatic Polymers and Pyridinium Polycation

et al. 2020

View full text Add to dashboard Cite

The effect of a range of synthetic charged polymers on alpha-synuclein aggregation and amyloid formation was tested. Sulfated aromatic polymers, poly(styrene sulfonate) and poly(anethole sulfonate), have been found to suppress the fibril formation. In this case, small soluble complexes, which do not bind with thioflavin T, have been formed in contrast to the large stick-type fibrils of free alpha-synuclein. Sulfated polysaccharide (dextran sulfate), as well as sulfated vinylic polymer (poly(vinyl sulfate)) and polycarboxylate (poly(methacrylic acid)), enhanced amyloid aggregation. Conversely, pyridinium polycation, poly(N-ethylvinylpyridinium), switched the mechanism of alpha-synuclein aggregation from amyloidogenic to amorphous, which resulted in the formation of large amorphous aggregates that do not bind with thioflavin T. The obtained results are relevant as a model of charged macromolecules influence on amyloidosis development in humans. In addition, these results may be helpful in searching for new approaches for synucleinopathies treatment with the use of natural polymers.

show abstract

“…Such antibodies are currently under clinical trials for Alzheimer’s disease [ 6 ]. Information is available on anti-amyloid activity of other macromolecular compounds including synthetic ones, such as polyelectrolytes, dendrimers, and others [ 7 , 8 , 9 , 10 , 11 ]. Ultimately, the use of macromolecular compounds interacting with target proteins at multiple sites, forming different types of bonds, increases recognition specificity.…”

Section: Introductionmentioning

confidence: 99%

Natural and Synthetic Derivatives of Hydroxycinnamic Acid Modulating the Pathological Transformation of Amyloidogenic Proteins

et al. 2020

View full text Add to dashboard Cite

This review presents the main properties of hydroxycinnamic acid (HCA) derivatives and their potential application as agents for the prevention and treatment of neurodegenerative diseases. It is partially focused on the successful use of these compounds as inhibitors of amyloidogenic transformation of proteins. Firstly, the prerequisites for the emergence of interest in HCA derivatives, including natural compounds, are described. A separate section is devoted to synthesis and properties of HCA derivatives. Then, the results of molecular modeling of HCA derivatives with prion protein as well as with α-synuclein fibrils are summarized, followed by detailed analysis of the experiments on the effect of natural and synthetic HCA derivatives, as well as structurally similar phenylacetic and benzoic acid derivatives, on the pathological transformation of prion protein and α-synuclein. The ability of HCA derivatives to prevent amyloid transformation of some amyloidogenic proteins, and their presence not only in food products but also as natural metabolites in human blood and tissues, makes them promising for the prevention and treatment of neurodegenerative diseases of amyloid nature.

show abstract

Complexes between cationic pyridylphenylene dendrimers and ovine prion protein: do hydrophobic interactions matter?

Abstract: MD simulation predicted the possible binding sites for the dendrimer interactions with protein while ITC data revealed both electrostatic and hydrophobic driving forces for the complexation.

Cited by 20 publications

References 61 publications

Protein Interaction with Charged Macromolecules: From Model Polymers to Unfolded Proteins and Post-Translational Modifications

Protein Interaction with Charged Macromolecules: From Model Polymers to Unfolded Proteins and Post-Translational Modifications

Alpha-Synuclein Amyloid Aggregation Is Inhibited by Sulfated Aromatic Polymers and Pyridinium Polycation

Natural and Synthetic Derivatives of Hydroxycinnamic Acid Modulating the Pathological Transformation of Amyloidogenic Proteins

Contact Info

Product

Resources

About