ProteoKnot tackles a fundamental challenge in molecular design: the current inability to create synthetic molecules with dynamic, protein-like tertiary structures. In nature, the functions of biomolecules such as proteins rely on their ability to adopt complex, flexible three-dimensional conformations. In contrast, synthetic systems are typically limited to simpler, rigid secondary structures, like single helices. To overcome this limitation, ProteoKnot introduces a novel approach that uses molecular entanglements to control both the shape and flexibility of synthetic macromolecules.
The project is structured around three main objectives. First, we are developing design principles for constructing multiply entangled molecular architectures, referred to as “entangled tertiary folds”. These principles are tested on multi-stranded helices (WP1), then applied to more complex structures including entangled macromolecules (WP2) and polymers (WP3). Second, we are incorporating photoswitchable elements (azobenzene units) into these systems to enable remote, reversible control over their conformations (WP4). At a later stage of the project, we will demonstrate the functional potential of these dynamic structures by developing multi-responsive catalysts that mimic key aspects of protein behavior (WP5).
ProteoKnot aims to significantly advance the fields of synthetic foldamers and molecular topology by enabling the synthesis of dynamic, programmable tertiary structures. The outcomes of this project could open new avenues for designing adaptive molecular machines, smart catalysts, and functional materials, offering a powerful alternative to current bioinspired approaches and expanding the toolbox of molecular nanotechnology.
