Evolution versus design: Template-directed self-assembly of peptides to artificial proteins (TASP)

Protein design and mimicry combines elements of synthetic organic chemistry with structural and functional aspects of biological relevance in a unique way. Due to progress in this interdisciplinary research field, access to m olecules featuring some essential properties of native proteins appears to be within reach, enabling the complex mechanisms in molecular recognition p rocesses to be deciphered. Since its introduction by the authors, the templ ate approach in protein de novo design (Template Assembled Synthetic Protei ns, TASP) has experienced a broad conceptual diversification. Starting from today's state-of-the-art in protein design, we present here some ongoing w ork in the Lausanne laboratories focusing on the use of regioselectively ad dressable tem plates and TASP scaffolds for addressing fundamental question s in peptide assembly, protein folding and mimicry. It is shown that the de veloped concepts can ideally reconcile evolutionary and rational design pri nciples for creating molecules of biological and therapeutic interest.