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 concerted mechanism involving the two groups of the handle. Furthermore, reduction of the disulfide bond, performed with tris-carboxyethyl phosphine, quantitatively releases beta-mercaptoester peptides suitable for biochemical applications (e.g., coupling to protein carriers). Another promising route for peptide release was found: beta-mercaptoester peptides gave, in slightly basic conditions, the C-terminal free-form peptide in good yields and purities. Finally, classical ester cleavage performed with OH or NH3 led to C-terminal free-form or amide peptides, respectively.
Brugidou
J
J
UPR 9008 CNRS-U 249 INSERM, Montpellier, France.
Méry
J
J
D000595:Amino Acid Sequence; D000812:Anhydrides / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D004355:Drug Stability; D004952:Esters / Q000737:chemistry; D005240:Feasibility Studies; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000812:Anhydrides; D003432:Cross-Linking Reagents; D004220:Disulfides; D004952:Esters; D010455:Peptides; C088075:2-hydroxypropyldithio-2'-isobutyric acid