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Supramolecular Chemical Biology Modulation of Protein-Protein Interactions

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The potential of the supramolecule

Flexible, rapidly adapting protein-protein interactions are essential for the control of biological reactions. The amazing dynamics of living systems are probably due in part to the self-assembling supramolecule.

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Beyond the domain of traditional molecular chemistry, where molecules are held together with relatively strong covalent bonds is the supramolecular assembly. Held together by weak bonds, the molecules in a supramolecular system are readily added and taken away for changes in size, shape and composition depending on the target molecules. The SUPRACHEMBIO (Supramolecular chemical biology modulation of protein-protein interactions) project has taken the concepts of supramolecular chemistry to study and modulate biological phenomena. The focus was on two fundamental processes – dimerisation and its reversal (where a compound is made up of two simpler molecules) and immobilisation of proteins. Researchers developed synthetic host-guest (enzyme-substrate) systems based on cyclodextrins to induce or stabilise protein heterodimerisation. They also set up cucurbitol-based systems to investigate homodimerisation. These allosteric modulators of protein dimerisation demonstrate highly efficient reversible enzyme activation as well as controlled immobilisation of proteins for a range of bionanotech applications. Self-assembling supramolecular structures that are modular are ideal for the flexible display of multifunctional biological ligands. Architectures with columnar and spherical geometries were developed and these covered basic but crucial biological functions such as protein assembly on a supramolecular framework and recognition for entry into cells. The SUPRACHEMBIO building block approach to design and fabricate supramolecules in biological systems has a wide range of applications with high bio-impact. Areas in nanobiotech that could benefit include pharma, synthetic enzyme systems for biomolecule synthesis and targeted medicine.

Keywords

Self-assembling supramolecule, dimerisation, enzyme activation, nanobiotech

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