The Process of Denaturation and Renaturation of Proteins. Linus Pauling. May 26, 1941

Proteins under the influence of certain conditions or reagents undergo certain changes; this process is called denaturation. Thus many naturally occurring proteins have certain specific properties - hemoglobin can combine with oxygen, pepsin can proteclize other proteins, etc. On denaturation these specific properties are lost in whole or in part.

It has been known for some years that some proteins after denaturation can, by the slow removal of the denaturating condition or reagent, be renatured to essentially their original form. This has been done, for example, by Anson and Mirsky for hemoglobin and trypsin.

A new idea is that proteins by suitable treatment may be denatured and then renatured to produce substances different from the original proteins, and with different properties. I was led to this idea by theoretical considerations. So far as I know, no one else has ever expressed the idea. An important feature of this treatment is that it avoids the undesirable properties (insolubility, etc.) resulting from denaturation alone.

Because of the extensive occurrence and use of proteins and their great importance to life and industry, there is the possibility that this proposed general method of treating a protein in such a way as to convert it into a substance with new and different properties may be of practical value. Some possible examples of usefulness are the following.

1. A normal protein might by suitable treatment be given a configuration complementary to that of another protein or other substance; that is, converted into a specific antibody to it. This suggestion is discussed further separately.

2. A native protein might be so changed as to lose certain immunological properties, without being otherwise denatured, permitting it to be used by patients who are sensitive to the original protein.

3. In particular this process might be carried out on serum or plasma fractions or other proteins used for transfusions, decreasing the danger of sensitization and shock.

4. A protein to which a patient is sensitive might be treated in such a way as to change to change in part its immunological properties, permitting it to be used more effectively and safely in desensitizing the patient.

5. The process might be applied to blood in such a way as to change the oxygen-combining power of hemoglobin and to make it more useful to certain patients.

6. The digestibility of a food protein might be increased by this treatment.

7. The solubility or other physical properties of a protein might be changed by this treatment in such a way as to make it more useful.

8. A protein might by suitable treatment be given the power of combining with some chemical substance and thus acting as a carrier for this substance or increasing its solubility or combining with it to diminish its activity.

9. The enzymatic activity of a protein might be usefully increased or changed or decreased by this treatment.