Protein secondary structure templates derived from bioactive natural products. Combinatorial chemistry meets structure-based design

Lead finding strategies in pharmaceutical research comprise structure-based drug design as well as screening efforts of natural product pools or large chemical libraries. In this context we propose a combined approach by utilizing natural product-derived structure information on receptor- or enzyme-complementary for designing unique core structures that can be employed as privileged template molecules underlying combinatorial libraries. A set of rules for the transformation of molecular frameworks from natural products to structurally defined peptidomimetics is introduced. Special emphasis is laid on the correspondence in the orientational properties and functionalization patterns between natural products and regular protein secondary structures.