2-HYDROXYPROPYL-DITHIO-2'-ISOBUTYRIC ACID (HPDI) AS A MULTIPURPOSE PEPTIDE-RESIN LINKER FOR SPPS

A new type of bifunctional handle for solid-phase peptide synthesis is described that contains both a disulfide and an ester group. Several peptides up to 22 residues long were assembled Our results demonstrate the stability of this bifunctional handle in the repetitive steps of the Fmoc/tBu protocol and in the corresponding side-chain deprotection conditions. New ways of peptide release were investigated. Cyanolysis in mild conditions led to a C-terminal free-form peptide by a concert ed mechanism involving the two groups of the handle. Furthermore, redu ction of the disulfide bond, performed with tris-carboxyethyl phosphin e, quantitatively releases beta-mercaptoester peptides suitable for bi ochemical applications (e.g., coupling to protein carriers). Another p romising route for peptide release was found: beta-mercaptoester pepti des gave, in slightly basic conditions, the C-terminal free-form pepti de in good yields and purities. Finally, classical ester cleavage perf ormed with OH- or NH3 led to C-terminal free form or amide peptides, r espectively.