Insulin, disulfide bridges sequence determination

Probably the most important achievement in insulin research was the determination of its primary structure by Frederick Sanger and his associates in Cambridge, England. In order to elucidate the amino acid sequence of the hormone it was necessary to separate the two chains constituting the molecule. This was accomplished by oxidation with performic acid. This operation cleaved the three disulfide bridges by converting each cystine to two cysteic acid residues ... 

Both intrachain and interchain disulfide bridges are present in insulin (cf. Table 3, p. 7) and it is obvious that determination of the sequence of the two chains had to be preceded by their separation. 

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