Solid‐Supported Synthesis of Highly Functionalized Tripodal Peptides with Flexible but Preorganized Geometry: Towards Potential Serine Protease Mimics

Abstract

Abstract Tripodal scaffold 1 has been used in the synthesis of a representative member of a library of serine protease mimics, possessing three independent functionalized peptide chains on a central core. Each peptide chain contains one residue of the classical catalytic triad (serine, histidine and aspartate) found in the active site of the serine protease α‐chymotrypsin. A particular feature of the novel tripodal design is its essentially flexible yet preorganized structure as deduced from molecular modeling studies. The choice of suitable scaffold and side‐chain protecting groups was intensively studied and optimized to ensure complete orthogonality. Inclusion of a photolabile linker enabled the release of intermediates and final structures from the solid‐support polymer allowing positive evaluation of the present strategy for the synthesis of future tripodal libraries of serine protease mimics.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)