Peptides are chains of amino acids linked by covalent chemical bonds to form folded three-dimensional structures. They are the basic building blocks of proteins that have a variety of biological functions including catalysis, blocking, immunization and signal transduction.
The development of solid-phase peptide synthesis (SPPS) in the early 1950s made peptides more practical for a wide range of applications and led to the current worldwide industry of peptide-based therapeutics. The key advantage of SPPS is that it retains the chemistry that takes place in solution but adds a step that links the nascent peptide chain to a macroscopically insoluble solvent-swollen resin support. This allows the chain to be reacted with other amino acid derivatives without having to isolate and elute the product from each reaction. It also circumvents the comparatively time-consuming cleavage of the peptide from the resin after each synthesis cycle.
This is a rapid and efficient method, with the advantage that it provides greater control over the structure of the final peptide compared to conventional solution-phase methods. The resulting products are highly purified and can be delivered as crude or lyophilized powders.
Successful peptide synthesis depends on the selection of the solid support, linker (between the solid support and the synthesized peptide), appropriately protected amino acids, coupling methodology and a protocol for cleaving the peptide from the solid support. It is essential to ensure that the peptide has been characterized by liquid chromatography-mass spectrometry to identify any contaminants that may adversely affect its clinical efficacy and safety. These impurities can originate from the starting materials, manufacturing process or storage conditions and can be difficult to control.