Tartric acid-based linker for the solid-phase synthesis of C-terminal peptide alpha-oxo aldehydes

A novel linker, based on the anchoring of (+)-dimethyl 2,3-O-isopropylidene -D-tartrate to PEGA or PEG-PS solid supports, was developed for the solid-p hase synthesis of C-terminal peptide alpha -oxo aldehydes. Peptide elongati on was performed using the 9-fluorenylmethoxycarbonyl/t-Bu chemistry. The p eptide and the 1,2-diol were deprotected on the solid phase. Then, a period ic oxidation of the fully deprotected peptidyl-resin led to the simultaneou s cleavage of the product from the solid support and to the generation of t he alpha -oxo aldehyde moiety. The methodology allowed the distance between the alpha -oxp aldehyde and the peptide to be easily modulated. The C;term inal peptide alpha -oxo aldehydes synthesized in this study were found to b e useful partners in hydrazone, thiazolidine, and oxime chemical ligations.