Investigating possible changes in protein structure during dendrimer–protein binding

Chiba, Fumiko; Mann, G.; Twyman, Lance J.

doi:10.1039/c0ob00041h

Cited by 12 publications

(27 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Twyman and coworkers designed polyanionic poly(amidoamine) (PAMAM) dendrimers which bind to Cyt c and -chymotrypsin. 69,70 PAMAM dendrimers have also been shown to bind to human serum albumin in an extensive study by the Giri group. 71 They studied binding constants, NMR ( 1 H, STD and DOSY) and molecular dynamic (MD) simulations of 19 PAMAM dendrimers in order to gain insight into the interactions, looking at differences in core, dendrimer generation and terminal group permitting detailed analyses of the key determinants of protein recognition.…”

Section: Dendrimersmentioning

confidence: 99%

Metal complexes as “protein surface mimetics”

Hewitt

Wilson

2016

Chem. Commun.

View full text Add to dashboard Cite

A key challenge in chemical biology is to identify small molecule regulators for every single protein. However, protein surfaces are notoriously difficult to recognise with synthetic molecules, often having large flat surfaces that are poorly matched to traditional small molecules. In the surface mimetic approach, a supramolecular scaffold is used to project recognition groups in such a manner as to make multivalent non-covalent contacts over a large area of protein surface. Metal based supramolecular scaffolds offer unique advantages over conventional organic molecules for protein binding, inlcuding greater steroechemcial and geometrical diversity conferred through the metal centre and the potential for direct assessment of binding properties and even visualisation in cells without recourse to further functionalisation. This feature article will highlight the current state of the art in protein surface recognition using metal complexes as surface mimetics.

show abstract

Section: Dendrimersmentioning

confidence: 99%

Metal complexes as “protein surface mimetics”

Hewitt

Wilson

2016

Chem. Commun.

View full text Add to dashboard Cite

show abstract

“…Charged dendrimers bound to a protein's interfacial area without affecting the protein's secondary structure [43] Actin Cationic poly(lysine) dendrimers 3 types of interactions: (a) at low concentration (0.01-1 g/ml) dendrimers behaved like G-actin-binding protein; (b) at higher concentrations (10 g/ml) they accelerated the time course in the exponential phase; (c) in the range 10-100 g/ml they accelerated the polymerization by shortening both the lag phase and exponential phase.…”

Section: Collagenmentioning

confidence: 99%

“…These 'sites' are based on local concentrations of charged amino acid residues at the protein surface [42]. In 2010, Chiba et al [43] proposed a 'hot spot' model of dendrimer-protein interactions also based on 'hot spots' of a protein globule that bound dendrimers. In this model (Fig.…”

Section: Modeling Of Dendrimer-protein Interactionsmentioning

confidence: 99%

Dendrimer-protein interactions versus dendrimer-based nanomedicine

Shcharbin

Shcharbina²,

Dzmitruk

et al. 2017

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

Dendrimers are hyperbranched polymers belonging to the huge class of nanomedical devices. Their wide application in biology and medicine requires understanding of the fundamental mechanisms of their interactions with biological systems. Summarizing, electrostatic force plays the predominant role in dendrimer-protein interactions, especially with charged dendrimers. Other kinds of interactions have been proven, such as H-bonding, van der Waals forces, and even hydrophobic interactions. These interactions depend on the characteristics of both participants: flexibility and surface charge of a dendrimer, rigidity of protein structure and the localization of charged amino acids at its surface. pH and ionic strength of solutions can significantly modulate interactions. Ligands and cofactors attached to a protein can also change dendrimer-protein interactions. Binding of dendrimers to a protein can change its secondary structure, conformation, intramolecular mobility and functional activity. However, this strongly depends on rigidity versus flexibility of a protein's structure. In addition, the potential applications of dendrimers to nanomedicine are reviwed related to dendrimer-protein interactions.

show abstract

“…10 Additionally, we have shown that carboxylate terminated dendrimers do not affect or modify the conformation of the protein. 14…”

Section: Resultsmentioning

confidence: 99%

“…We were also able to demonstrate (using circular dichroism) that dendrimer/protein binding was not accompanied by changes in protein structure. 14 Although the principle interactions are electrostatic, proteins bind specifically and with high affinity because of additional non-covalent interactions provided by the amino acid functionality.…”

Section: Introductionmentioning

confidence: 99%

Effect of Terminal-Group Functionality on the Ability of Dendrimers to Bind Proteins

Chiba

Twyman

2017

Bioconjugate Chem.

View full text Add to dashboard Cite

It is known that dendrimers can bind proteins with good selectively. This selectivity comes about from an optimization based on matching the size of the dendrimer with the size of the protein's interfacial binding area. In this paper, we report how this selectivity can be moderated by the functionality on the surface of the dendrimer. Specifically, we describe the synthesis of amino acid functionalized dendrimers and the effect of functionality on the dendrimer's ability to bind and inhibit the enzymatic protein, chymotrypsin. The results show how dendrimer binding can be increased or decreased depending on the terminal functionality. These results will allow new ligands to be designed and synthesized, possessing increased and selective protein-binding abilities.

show abstract

Investigating possible changes in protein structure during dendrimer–protein binding

Cited by 12 publications

References 30 publications

Metal complexes as “protein surface mimetics”

Metal complexes as “protein surface mimetics”

Dendrimer-protein interactions versus dendrimer-based nanomedicine

Effect of Terminal-Group Functionality on the Ability of Dendrimers to Bind Proteins

Contact Info

Product

Resources

About