Letter | Published:

Specificity of Pepsin and its Dependence on a Possible ‘Hydrophobic Binding Site’

Naturevolume 199pages10941095 (1963) | Download Citation



THE specificity of pepsin has been extensively investigated, and the information obtained from work using synthetic di- or tri-peptides indicates that pepsin preferentially hydrolyses peptides which contain a tyrosine or phenylalanine residue1,2. However, Sanger, using the A and B chains of insulin, found that peptide linkages which did not involve tyrosine or phenylalanine were hydrolysed by pepsin3,4. Bovey and Yanari5 recently reviewed the action of pepsin on synthetic peptides and proposed several general rules. It was pointed out, however, that these rules “do not necessarily apply to the peptic digestion of proteins and large polypeptides, which is often considerably more extensive than these rules would lead one to expect”. In order to understand the action of pepsin on protein substrates, we have made a systematic examination of the sequence of amino-acid residues adjacent to the site of peptic hydrolysis in several proteins of known amino-acid sequences. In this communication, a concept is proposed which explains the specificity of pepsin for protein substrates in terms of a hypothetical ‘hydrophobic binding site’.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Fruton, J. S., Bergmann, M., and Anslow, jun., W. P., J. Biol. Chem., 127, 627 (1939).

  2. 2

    Baker, L. E., J. Biol. Chem., 193, 809 (1951).

  3. 3

    Sanger, F., and Tuppy, H., Biochem. J., 49, 481 (1951).

  4. 4

    Sanger, F., and Thompson, E. O. P., Biochem. J., 53, 366 (1953).

  5. 5

    Bovey, F. A., and Yanari, S. S., in The Enzymes, edit. by Boyer, P. D., Lardy, H., and Myrback, K., 5, 63 (Academic Press, New York, 1960).

  6. 6

    Li, C. H., Symposium on Protein Structure, edit. by Neuberger, A., 302 (John Wiley, Inc., New York, 1958).

  7. 7

    Hirs, C. H. W., Moore, S., and Stein, W. H., J. Biol. Chem., 235, 633 (1960).

  8. 8

    Konigsberg, W., and Hill, R. J., J. Biol. Chem., 237, 3157 (1962).

  9. 9

    Némethy, G., and Scheraga, H., J. Phys. Chem., 66, 1773 (1962).

  10. 10

    Cohn, E. J., and Edsall, J. T., Protein, Amino Acids and Peptides (Reinhold Pub. Corp., New York, 1943).

Download references

Author information


  1. Oklahoma Medical Research Institute and Department of Biochemistry, University of Oklahoma School of Medicine, Oklahoma City

    • J. TANG


  1. Search for J. TANG in:

About this article

Publication history

Issue Date



Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.