BIFUNCTIONAL SCAFFOLDS AS TEMPLATES FOR SYNTHETIC COMBINATORIAL LIBRARIES

A small-molecule synthetic combinatorial library was designed and synt hesized that features potential pharmacophores attached to a variety o f small cyclic scaffolds. The synthesis of the library involved random ization of three types of building blocks: 20 amino acids, 10 aromatic hydroxy acids and 21 alcohols, totaling a library complexity of 4200 compounds. Mitsunobu polymer-supported etherification was used in the last randomization. The library compounds were attached to beads via a n ester-bond linkage enabling both on-bead as well as in-solution scre ening. When the library was tested against a model target, streptavidi n, specific binders were found. The structures of the most active comp ounds were determined from the fragmentation pattern in MS/MS experime nts.