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Re-designing zinc finger proteins by swapping alpha-helical domains with foldamer helices (LXWAP)
Date du début: 11 mars 2013, Date de fin: 10 mars 2015 PROJET  TERMINÉ 

"Alpha-helices (aHs) are recurrent structures in proteins, whose folding properties, stability and function have been widely investigated. They often play the key role of recognition elements between proteins, or proteins and nucleic acids. These interactions are generally regulated by the strategic presentation of a few key residues on their surface. The efforts of many groups have been devoted to the synthesis of artificial molecules (foldamers), to mimic the structural complexity of natural helices, with the aim to reproduce their functions. A number of foldamer backbones has been synthesized to date, and their predictability and tunability constitute a great potential for their future applications. However, attaining more complex tertiary/quaternary structures through foldamers is still partially unaccomplished, and constitutes one of the ultimate goals in the field. This project will move a step forward towards the realization of this mission, by creating new composite proteins, swapping aHs with oligourea helices. The first target will be zinc fingers, a well described class of metalloproteins specialized in nucleic acid binding. Their peculiar folding, extensive structural characterization and biological relevance will be an ideal starting point to study the influence of the replacement of aHs with foldamers in this complex machinery. The new composite proteins will be tested to obtain insights into folding, metal complexation, DNA binding ability and cellular behavior of these new entities. This project will form a bridge between the expertise of the applicant in the chemistry of DNA targeting, and the host in oligourea foldamers. A further collaboration with a specialist in metallopeptides will provide the appropriate combination of knowledge required for this multidisciplinary study. This technology will be a milestone in the design of composite proteins and their use in the modulation of protein characteristics, with possible biomedical applications."

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