Protein semisynthesis with the help of mixed anhydrides and enzymes: chemistry and synthesis of insulins

Proteins play a prominent role in nature and their biosynthesis occurs via stepwise combination of amino acids. One can imitate this method in laboratory or synthesize the polypeptide chain by combining smaller preformed fragments (fragment condensation). Reversible protection of reactive groups and solubility problems arising are the most important features in this regard. Semisynthesis, i.e., coupling of amino acids or peptides to natural material may help to overcome these difficulties. The preparation of hybrid preproinsulin by mixed anhydride synthesis and the conversion of pork insulin to human insulin by enzyme-catalyzed peptide synthesis are two examples of the semisynthesis of proteins. In both cases optimal reaction conditions are essential for maximal yield of the product desired. In spite of the rapid improvement of gene technology, chemical peptide synthesis will retain its value for the preparation of biologically and pharmacologically interesting substances.