Towards Functional Peptide-Based Supramolecular Structures

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Towards Functional Peptide-Based Supramolecular Structures*******Inspired by natural sophisticated proteic systems, our research program aims at developing functional supramolecular structures exploiting polypeptide as molecular framework. For the next grant period, we propose to devote our efforts into four areas:***1. Use artificial ion channels as sensing devices****We will pursue our development of crown ether peptide-based ion channels towards sensing devices. Several biological recognition elements will be introduced at the N-terminal position to study and eventually to detect the presence of specific biomarkers and cells. ***2. Preparing fluorinated channels and nanopores ****We will synthesize fluorinated helical peptides and study their self-assembly into novel supramolecular architectures driven by fluorine-fluorine interactions. Such superstructures will create fluor-lined channels and nanopores. We intend to study membrane ion transport properties of those fluorinated channels to understand the structural features essential for ion translocation.***3. Developing antimicrobial peptide nanostructures****Towards novel and efficient antimicrobials against resistant bacteria, we have used a de novo approach based on a simple 14 residue peptide. We propose to engineer systematically this model peptide with specific functional groups and to study their antimicrobial activities towards important pathogens. Modifications at terminal positions and in the sequence will be evaluated with respect to their impact on bioactivity.***4. Biomimetic supramolecular catalysis in water****To catalyze efficiently industrially relevant organic transformations in water, we propose to synthesize a variety of peptide structures that can acts as supramolecular catalysts, hence mimicking natural enzymes. We will investigate several peptidic systems; from small rigid cyclic peptides, to conformationally biased oligopeptides. Different transformations will be studied as model reactions. Factors influencing efficiency will be identified with the goal of delineating design principles for developing biomimetic catalysts for a huge variety of transformations in water.