A peptide is a chain of two or more amino acids linked together by an amide bond. Typically, peptides consist of 2 to 70 amino acids in a linear sequence. Unlike proteins, peptides do not necessarily need to be folded to exhibit biological activity. These molecules are naturally present as peptide hormones, such as angiotensin and enkephalin, or as toxins in both plants and animals. Peptides hold significant importance as potential lead compounds in drug discovery and can also serve as drugs on their own. Their applications extend to fields like vaccines, biomaterials, histological probes, and they are extensively utilized as antigens for antibody generation.

Chemical synthesis of peptides is accomplished either in solution or on a solid support. The process involves the controlled and specific creation of an amide bond between an N-protected amino acid and another amino acid bearing a free amino group and protected carboxylic acid. In solid-phase peptide synthesis (SPPS), the carboxyl protecting group is attached to a polymer support. After forming the bond, the protecting group on the amino end of the dipeptide is removed, and the subsequent N-protected amino acid is linked. SPPS is the prevailing method for peptide synthesis due to its efficiency, ease, rapidity, and capability for parallel processing. It entails sequential addition of protected amino acid residues, both amino and side-chain protected, to a peptide or amino acid connected to an insoluble polymeric support.

For N-α protection, either an acid-labile Boc group (Boc SPPS) or a base-labile Fmoc group (Fmoc SPPS) is employed. Upon removing this protective group, the next amino acid, also protected, is introduced using a coupling reagent or a pre-activated protected amino acid derivative. The C-terminal amino acid is attached to the resin via a linker that governs the conditions for releasing the peptide from the support upon extending the chain. Often, side-chain protecting groups are chosen such that they are cleaved simultaneously during the detachment of the peptide from the resin. The Fmoc method is commonly preferred, as final cleavage and deprotection can be achieved with trifluoroacetic acid, unlike the Boc method, which necessitates the use of hazardous, corrosive anhydrous HF and specialized equipment.

Although peptides containing up to 50 amino acids can be routinely synthesized, reports of protein synthesis exceeding 100 amino acids are also prevalent. Longer proteins are produced using native chemical ligation of fully deprotected peptides in solution. This technique enables the synthesis of challenging natural peptides, the incorporation of unnatural or D-amino acids, and the creation of cyclic, branched, labeled, and post-translationally modified peptides.

While liquid-phase peptide synthesis, often utilizing Boc or Z-amino protection, has been largely replaced by solid-phase peptide synthesis, it is still employed for industrial-scale peptide production.