Solid-phase Synthesis - Solid-phase Synthesis of Peptides

Solid-phase Synthesis of Peptides

Solid-phase synthesis is the most common technique for peptide synthesis. Usually, peptides are synthesized from the carbonyl group side (C-terminus) to amino group side (N-terminus) of the amino acid chain in this method, although peptides are synthesised in the opposite direction in cells. In peptide synthesis, an amino-protected amino acid is bound to a solid phase material (most commonly, low cross-linked polystyrene beads), forming a covalent bond between the carbonyl group and the resin, most often an amido or an ester bond. Then the amino group is deprotected and reacted with the carbonyl group of the next amino-protected amino acid. The solid phase now bears a dipeptide. This cycle is repeated to form the desired peptide chain. After all reactions are complete, the synthesized peptide is cleaved from the bead.

The protecting groups for the amino groups mostly used in the peptide synthesis are 9-fluorenylmethyloxycarbonyl group (Fmoc) and t-butyloxycarbonyl (Boc). The Fmoc group is removed from the amino terminus with base while the Boc group is removed with acid.

Many amino acids bear functional groups in the side chain. In order to prevent these functional groups from reacting with the incoming N-protected amino acids, a number of other protecting groups specific for the amino acid to be protected is used. In contrast to BOC and Fmoc groups, these have to be stable over the course of peptide synthesis although they are also removed during the final deprotection of peptides.