Pepsin was later found to be an effective treatment for digestive disorders. Through this important application, efforts to produce and purify it greatly increased, and were successful by the end of the nineteenth century (Tang 1998).
At that time, however, the chemical nature and properties of enzymes as proteins were not completely understood. It was not until John H. Northrop crystallized pepsin in 1930, an achievement for which he shared the Nobel Prize in 1946, that the protein nature of enzymes was established (Manchester 2004).
After the Nobel Prize was awarded to Northrop, Sumner, and Stanley in 1946, new separation methods including crystallization and chromatography were further developed. Through these methods, the amino acid sequences of pepsin and pepsinogen were determined (Tang 1973).
Pepsin B and C were first isolated from porcine stomach by Ryle and Porter in 1959.
As X-ray diffraction techniques improved through the mid-1970s, the three-dimensional structure of pepsin was determined, allowing for a better understanding of the catalytic reaction (Fruton 2002).
Recently, interest in pepsin-type enzymes and their inhibitors has been renewed due to the recognition