Solid phase peptide synthesis, originally developed by Bruce Merrifield in 1963, has proven to be a major enabling tool for the creation of peptide sequences. Synthesis of a peptide chain on a solid support offers separation from soluble reagents and simple filtration and washing steps. However, byproducts from incomplete couplings, side reactions, and impurities can build up on the solid support with the desired product. Peptides are composed of amino acids, which are chemically linked together through a peptide bond.

The basic steps for the creation of a peptide on a resin are:

Deprotection - this process removes the Fmoc group from the N-terminus of the growing peptide chain and permits the next amino acid to be coupled.

Wash - the resin containing the peptide is washed thoroughly with solvent several times to completely clean the resin before beginning the coupling reaction.

Coupling - an amino acid is added to the peptide chain. This process requires activation of the amino acid before it can be connected to the growing peptide chain.

Wash - the resin containing the peptide is washed thoroughly with solvent several times to completely clean the resin before beginning the deprotection reaction of the next cycle.

Note: Steps 1 through 4 are repeated until the desired peptide sequence is assembled on the resin. The last step is to cleave the peptide from the resin and collect it.

Cleavage - the peptide is cleaved from the resin.