Solid Phase Synthesis of C-Terminal Peptide Aldehydes

Abstract

Peptides with C-terminal aldehydes (PAs) are of interest due to their inhibitory properties toward numerous classes of proteolytic enzymes. In this paper, we describe and compare two novel approaches for the preparation of PAs by solid phase synthesis, one based on the reduction of the Weinreb amide and the other on the reduction of phenyl esters. A study showed that purification of the PAs by chromatography (silica gel or reversed phase) induced a loss of the optical integrity of the C-terminal residue. Both methods were found to be suitable for the synthesis of PAs which were then used for the preparation of reduced-bond-containing peptides on insoluble polymers. The Weinreb amide approach was preferred for the synthesis of PAs due to an uncontrolled over-reduction of phenyl esters in our hands.