Letter | Published:

Preparation of an Insulin A Chain Derivative with an Intact Intra-chain Disulphide Bond

Naturevolume 199pages10951096 (1963) | Download Citation



THE insulin molecule contains three disulphide bonds according to Sanger's structure formula1. Two of these connect the peptide chains; the third forms an intra-chain linkage between residues 6 and 11 on the A chain. Various authors have shown that there are differences in the reactivities of the three disulphide bonds2. However, in the presence of concentrated solutions of urea or guanidine hydrochloride complete cleavage is observed as well by oxidative sulphitiolytic as by reductive procedures with thioglycolate or 2-mercaptoethanol3. The recombination of completely reduced insulin chains by re-oxidation with air gave only low yields in the experiments of several groups of investigators4–6, in accordance with theoretical statistical calculations made by Kauzmann7.

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  1. 1

    Ryle, A. P., Sanger, F., Smith, L. F., and Kitai, R., Biochem. J., 60, 541 (1955).

  2. 2

    For details, see Cecil, R., and McPhee, J. R., Adv. Prot. Chem., 14, 351 (Academic Press, New York and London, 1959).

  3. 3

    Thompson, E. O. P., Biochim. Biophys. Acta, 53, 447 (1961).

  4. 4

    Dixon, G. H., and Wardlaw, A. C., Nature, 188, 721 (1960).

  5. 5

    Du, Y. C., Zhang, Y. S., Lu, Z. X., and Tsou, C. L., Scientia Sinica, 10, 84 (1961).

  6. 6

    Bailey, J. L., and Cole, R. D., J. Biol. Chem., 234, 1733 (1959).

  7. 7

    Kauzmann, W., Sulfur in Proteins, 93 (Academic Press, New York, 1959).

  8. 8

    Cecil, R., and Loening, U. E., Biochem. J., 76, 146 (1960). Cecil, R., and Wake, R. J., ibid., 82, 401 (1962).

  9. 9

    Brdička, R., Coll. Czech. Chem. Comm., 5, 238 (1933).

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  1. Technical High School, Aachen



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