A review with 56 refs. The creation of native-like macromols. in copying nature's way represents a fascinating challenge in protein chem. today. In the absence of detailed knowledge of the complex folding pathway, the ultimate goal in protein de novo design, the construction of artificial proteins with predetd. three-dimensional structure and tailor-made functions based on a defined, generally valid set of rules, appears to still be out of reach. With progress in synthesis strategies and biostructural characterization methods, topol. templates have become a versatile tool for inducing and stabilizing secondary and tertiary structures, such as protein loops, b-turns, a-helixes, b-sheets and a variety of folding motifs. In this article, we extend the concept of template-assembled synthetic proteins for the construction of protein-like topologies with multiply bridged, oligocyclic chain architectures termed locked-in tertiary folds that exhibit unique physicochem. and folding properties because of the highly confined conformational space. Furthermore, we show that some fundamental questions in protein assembly can be approached applying the template concept. Using covalent template trapping of self-assocd. peptide assemblies in aq. soln. the structural and phys. forces guiding protein folding, supramol. assembly and mol. recognition processes can be studied on a mol. level. [on SciFinder (R)]