Template assisted protein de novo design

The ultimate goal in protein de novo design is the Construction of artificial proteins exhibiting tailor-made structural and functional properties. To create nativelike macromolecules in copying nature's way has proven to be difficult because the mechanism of folding in its complexity has yet to be unravelled. In the present review we describe a conceptually different approach in protein design, the concept of template assembled synthetic proteins (TASP), in order to bypass the folding problem. Topological templates as "built-in" devices for the induction of welldefined folding topologies and progress in synthetic strategies, e.g. chemoselective ligation methods and the use of pseudo-prolines to enhance peptide solvation open the way for the design of more complex, and hence functional TASP molecules.