The synthesis of the A- and B-chains of insulin and their isolation in the S-sulfonate form were accomplished. Combination experiments between the synthetic A- and natural B-chain, the synthetic B- and the natural A-chain, and between the synthetic A- and B-chains generated insulin activity. The yield of the generated activity in all cases was within the range of the activity obtained when similarly treated natural A- and B-chains are combined. This work represents the first chemical synthesis of a naturally Occurring protein and constitutes a case in which the proposed primary structure of a protein has been confirmed ky chemical synthesis.

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