Topological templates as tool in molecular recognition and peptide mimicry: synthesis of a TASK library.

Topological templates disposing orthogonally protected reactive sites in defined spatial positions of a variable degree of flexibility can serve as a pool for the selective functionalization by groups thought to interact with an acceptor molecule. This strategy is exemplified by the chemo-selective ligation of amino-acid residues to a cyclic peptide as a structural motif (template-assembled side chains; TASK) applying the concept of combinatorial libraries. Binding assays to a monoclonal antibody allow for the delineation of a lead compound mimicking the structural features of a discontinuous epitope. The conceptually novel approach may serve as a tool in molecular recognition studies and in drug development.