Solid Phase Peptide Synthesis

One of the most common methods for synthesizing peptides is solid phase peptide synthesis (SPPS). In SPPS, the first amino acid is attached to an insoluble polymer support. Additional amino acids are then added stepwise to elongate the peptide chain still attached to the solid support. SPPS has several advantages over solution phase synthesis including easy purification by simple washing and the ability to produce peptides without protecting groups on most residues.

The most widely used solid supports are Peptide Synthesis functionalized with chlorotrityl or Wang resins. In the first step, the α-carboxyl group of the C-terminal amino acid is attached to the solid support through its side chain.

Subsequent amino acids are then coupled to the peptide chain through their amino group in a stepwise manner. Each amino acid is activated, usually by the addition of a carbodiimide reagent, and coupled to the growing peptide chain still attached to the support.

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