Selective Peptide Binding Using Facially Amphiphilic Dendrimers

Gomez-Escudero, Andrea; Azagarsamy, Malar A.; Theddu, Naresh; Vachet, Richard W.; Thayumanavan, S.

doi:10.1021/ja803082v

Cited by 47 publications

(46 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously reported that the most drastic change in the critical aggregation concentration (CAC) occurred from the monomer to G1-dendron; the CAC gain from the G1 to G2 dendron was relatively small. [4f,9,12] Therefore, we focused on the simpler G1 dendron for the studies outlined here. It is essential, however, that we confirm that the CAC for the G1 dendron 1 synthesized here is indeed in the micromolar range.…”

Section: Resultsmentioning

confidence: 99%

Guest‐Release Control in Enzyme‐Sensitive, Amphiphilic‐Dendrimer‐Based Nanoparticles through Photochemical Crosslinking

Raghupathi

Azagarsamy

Thayumanavan

2011

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Stimuli sensitive, facially amphiphilic dendrimers have been synthesized and their enzyme-responsive nature has been determined with dual fluorescence responses of both covalently conjugated and non-covalently bound reporter units. These dual responses are correlated to ascertain the effect of enzymatic action on micellar aggregates and the consequential guest release. The release of the guest molecule is conveniently tuned by stabilizing the micellar aggregates through photochemical crosslinking of hydrophobic coumarin units. This photo-crosslinking is also utilized as a tool to investigate the mode of enzyme-substrate interaction in the context of aggregate-monomer equilibrium.

show abstract

Section: Resultsmentioning

confidence: 99%

Guest‐Release Control in Enzyme‐Sensitive, Amphiphilic‐Dendrimer‐Based Nanoparticles through Photochemical Crosslinking

Raghupathi

Azagarsamy

Thayumanavan

2011

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

show abstract

“…In other words, these dendrimers are able to form micelle-type assemblies in an aqueous milieu and inverted micelle-type assemblies in apolar solvents, such as toluene. [12e,17] In contrast to classical amphiphilic dendrimers, [12a,d] the micellar assemblies from our dendrimers are formed through aggregation of several dendrimer molecules. This feature presents a unique opportunity for stimuli-induced disassembly in these dendrimers through disaggregation.…”

Section: Resultsmentioning

confidence: 99%

Accessing Lipophilic Ligands in Dendrimer‐Based Amphiphilic Supramolecular Assemblies for Protein‐Induced Disassembly

Yesilyurt

Ramireddy

Azagarsamy

et al. 2011

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Supramolecular nanoassemblies that respond to the presence of proteins are of great interest, as aberrations in protein concentrations represent the primary imbalances found in a diseased state. We present here a molecular design, syntheses, and study of facially amphiphilic dendrimers that respond to the presence of the protein, immunoglobulin G. It is of particular interest that the ligand functionality, utilized for causing the binding-induced disassembly, be lipophilic. Demonstration of binding with lipophilic ligands greatly expands the repertoire of binding-induced disassembly, since this covers a rather large class of ligand moieties designed for proteins and these provide specific insights into the mechanistic pathways that are available for the binding-induced disassembly process. Here, we describe the details of the binding induced disassembly, including the change in size of the assembly in response to proteins, concurrent release of noncovalently encapsulated guest molecules, and the specificity of the disassembly process.

show abstract

“…Dendrons of several generations containing a carboxyl moiety as the hydrophilic functionality and a decyl moiety as the hydrophobic functionality were synthesized and used to form inverse micelle type assemblies (Scheme 4) 62 with CACs of 50, 2.5, and 1 μM for G1, G2, and G3 dendrons, respectively.…”

Section: Supramolecular Assemblies For Peptide Extractionmentioning

confidence: 99%

Supramolecular Disassembly of Facially Amphiphilic Dendrimer Assemblies in Response to Physical, Chemical, and Biological Stimuli

et al. 2014

Self Cite

View full text Add to dashboard Cite

ConspectusSupramolecular assemblies formed from spontaneous self-assembly of amphiphilic macromolecules are explored as biomimetic architectures and for applications in areas such as sensing, drug delivery, and diagnostics. Macromolecular assemblies are usually preferred, compared with their simpler small molecule counterparts, due to their low critical aggregate concentrations (CAC) and high thermodynamic stability. This Account focuses on the structural and functional aspects of assemblies formed from dendrimers, specifically facially amphiphilic dendrons that form micelle or inverse micelle type supramolecular assemblies depending on the nature of the solvent medium.The micelle type assemblies formed from facially amphiphilic dendrons sequester hydrophobic guest molecules in their interiors. The stability of these assemblies is dependent on the relative compatibility of the hydrophilic and hydrophobic functionalities with water, often referred to as hydrophilic–lipophilic balance (HLB). Disruption of the HLB, using an external stimulus, could lead to disassembly of the aggregates, which can then be utilized to cause an actuation event, such as guest molecule release. Studying these possibilities has led to (i) a robust and general strategy for stimulus-induced disassembly and molecular release and (ii) the introduction of a new approach to protein-responsive supramolecular disassembly. The latter strategy provides a particularly novel avenue for impacting biomedical applications. Most of the stimuli-sensitive supramolecular assemblies have been designed to be responsive to factors such pH, temperature, and redox conditions. The reason for this interest stems from the fact that certain disease microenvironments have aberrations in these factors. However, these variations are the secondary imbalances in biology. Imbalances in protein activity are the primary reasons for most, if not all, human pathology. There have been no robust strategies in stimulus-responsive assemblies that respond to these variations. The facially amphiphilic dendrimers provide a unique opportunity to explore this possibility.Similarly, the propensity of these molecules to form inverse micelles in apolar solvents and thus bind polar guest molecules, combined with the fact that these assemblies do not thermodynamically equilibrate in biphasic mixtures, was used to predictably simplify peptide mixtures. The structure–property relationships developed from these studies have led to a selective and highly sensitive detection of peptides in complex mixtures. Selectivity in peptide extraction was achieved using charge complementarity between the peptides and the hydrophilic components present in inverse micellar interiors. These findings will have implications in areas such as proteomics and biomarker detection.

show abstract

Selective Peptide Binding Using Facially Amphiphilic Dendrimers

Cited by 47 publications

References 71 publications

Guest‐Release Control in Enzyme‐Sensitive, Amphiphilic‐Dendrimer‐Based Nanoparticles through Photochemical Crosslinking

Guest‐Release Control in Enzyme‐Sensitive, Amphiphilic‐Dendrimer‐Based Nanoparticles through Photochemical Crosslinking

Accessing Lipophilic Ligands in Dendrimer‐Based Amphiphilic Supramolecular Assemblies for Protein‐Induced Disassembly

Supramolecular Disassembly of Facially Amphiphilic Dendrimer Assemblies in Response to Physical, Chemical, and Biological Stimuli

Contact Info

Product

Resources

About