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ASPIRE Informe resumido

Project ID: 240629
Financiado con arreglo a: FP7-IDEAS-ERC
País: United Kingdom

Final Report Summary - ASPIRE (Aqueous Supramolecular Polymers and Peptide Conjugates in Reversible Systems)

Many advances in the field of supramolecular polymer assembly have been accomplished. Work has advanced from initial efforts to produce supramolecular block co-polymers from end-functionalised polymers using CB[8] to develop branched polymeric assemblies using side-appended first and second guests to produce high water percentage hydrogels. Further development of this work has allowed for the functionalisation of biologically compatible polymeric scaffolds with non-toxic side-appended guests, which complex with CB[8] in a 2:1 fashion to form hydrogels with great potential for in vivo drug delivery. The knowledge we developed for hydrogel formation has also been adapted to supramolecular microcapsules and hydrogel beads capable of cargo encapsulation and release. Systematic studies have also been conducted into understanding the basic physical dynamics of CB[8]- based hydrogels to enable greater understanding and thus control over their rheological properties. We have also incorporated our hydrogels into hybrid materials incorporating DNA hydrogels and nanofibrillated cellulose for new soft material scaffolds. Work has also been initiated in the field of photoresponsive CB[8]-based hydrogels and rhelogical-fluids using azobenzenes as second guests.

Stimuli-responsive supramolecular polymers have also been investigated and considerable success in photo- regulated assembly and disassembly of linear supramolecular polymers has been achieved. This work is currently being developed further by using SERS to monitor the in situ growth of such supramolecular components from monomeric subunits to extended components. Linear supramolecular block copolymers have also been incorporated into fluorescently-tagged vesicles capable of cargo uptake and stimuli-responsive release upon incorporation into HeLa cell lines.

Efforts into the dissagregation of high fluorescence quantum yield dyes in water via CB[8] complexation has also yielded promising results in the field of biocongugate fluorescent tags. This high impact work has also led to research into water-based energy transfer assemblies through orthogonal self-assembly incorporating CB[n]. We also aimed to use supramolecular chemistry in order to understand the structure and role of a number of protein oligomers associated with many life altering and life threatening diseases such as Parkinson's, Alzheimer's and type II diabetes. Our innovative approach allowed us to overcome some typical difficulties associated with the nature of the systems studied, such as solubility and tendency to aggregate and precipitate at high concentration. We successfully studied the effects of CB[n] on the aggregation rate of insulin, a protein associated with diabetes, and observed a novel and reversible pathway towards the aggregation and precipitation of this protein. We also demonstrated that CB[8] can be used to create ternary complexes with functionalised peptides and proteins. This ability enabled the synthesis of covalently-bound protein dimers in an unprecedented high yielding regime. Moreover, using CB[8] ternary complexes, we were able to study the effects that this macrocycle has on ABeta aggregation (Alzheimer's disease). Using our supramolecular approach we were able to demonstrate that CB[8] dramatically increases the rate of aggregation of the ABeta bypassing the toxic oligomeric state of ABeta and offering an alternative approach to counter Alzheimer's disease.

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United Kingdom
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