Peptidasynthese

Peptidasynthese, or peptide synthesis, is the chemical construction of peptides by linking amino acids or short fragment sequences with peptide bonds. The dominant approach is solid-phase peptide synthesis (SPPS), which was developed by Merrifield in 1963. In SPPS, the peptide chain is assembled while attached to an insoluble resin support. Two main protection strategies are used: Fmoc/tBu and Boc/Bzl. In Fmoc-SPPS, the N-terminal amino group is protected by Fmoc; deprotection is achieved with a base such as piperidine, leaving the side chains protected. Each amino acid is activated and coupled using reagents like HBTU, HATU, or DIC, often with a base to facilitate the reaction. Coupling cycles are repeated until the desired sequence is assembled. The completed peptide is then cleaved from the resin and globally deprotected by a cleavage cocktail, typically trifluoroacetic acid (TFA) with scavengers. The crude product is purified by high-performance liquid chromatography (HPLC) and characterized by mass spectrometry and, where needed, NMR.

Alternatives include solution-phase synthesis and fragment condensation, and modern workflows commonly employ automation and, increasingly, microwave-assisted heating to speed reactions. SPPS supports diverse modifications, including cyclic peptides, disulfide bonds, and post-synthetic labeling.

Applications span basic research, drug development, and diagnostics, with peptide therapeutics and vaccines as notable areas. Challenges include sequence complexity, racemization of certain residues, aggregation of long sequences, protecting-group management, and scale-up costs. Typical SPPS produces peptides from tens to hundreds of amino acids, though longer sequences require fragment coupling strategies.