Peptides were first synthesized around the turn of the century. During the following decades, the compounds found many applications. At present, both solid and liquid phase methods may be used to chemically formulate peptides. The formation of a peptide bond requires both activation and protection. Although these processes have a long history, researchers continue to search for better coupling reagents and improved protecting group strategies.
Curtius (1881) and Fischer (1902) were the first to synthesize simple peptide derivatives (2:1-8). About that time, Hofmeister (1902) and Fischer (1906) additionally recognized that proteins actually consist of amino acids linked together by amide bonds. Subsequent peptide research generally involved the synthesis of "small, well-defined peptides" which were used to study certain proteolytic enzymes (2:1-8).
Around the mid-20th century, researchers discovered biologically active peptides. Oxytocin was isolated in 1952. Shortly thereafter, investigators (du Vigneaud et al. 1953, Tuppy 1953) determined oxytocin's structure. In fact, the total synthesis of polypeptide (du Vigneaud et al. 1953) eventually helped motivate the development of more advanced synthetic procedures.
It wasn't until Sanger and associates (1953) demonstrated the structure of insulin, however, that the study of peptides became more pragmatic. Researchers recognized that they could synthesize significant quantities of physiologically potent compounds. In recent decades, many peptide hormones have been formulated. Some of these include insulin, human growth hormone, and luteinizing hormone releasing hormone. In addition, recombinant methods have been used to create tissue plasminogen activator and human erythropoietin.
The chemical syntheses of peptides generally involves the incorporation of amino acid residues into growing polypeptide chains. This may involve the following chemical s...