The ultimate goal in protein de novo design is the construction of art
ificial proteins exhibiting tailor-made structural and functional prop
erties. To create native-like macromolecules in copying nature's way h
as proven to be difficult because the mechanism of folding in its comp
lexity has yet to be unraveled. Ln order to bypass the well-known fold
ing problem, we have developed the concept of template assembled synth
etic proteins (TASP); this meanwhile widely accepted strategy uses top
ological templates as 'built-in' devices for the induction of well-def
ined folding topologies. Progress in synthetic strategies, e.g., chemo
sslective ligation methods and orthogonal protection techniques open t
he way for the design of more complex TASP molecules featuring functio
nal properties such as membrane channels, vaccines, catalysts. recepto
rs, or ligands.