Abstract
PORCINE insulin has only three amino groups, those of the terminal residues of the two chains (glycineA1, phenylalanineB1) and a side chain amino group (lysineB29)1. Many reagents have been developed to take advantage of the reactivity of the NH2 group in proteins—probably more than for any other functional group—and there have been many reports on the modification of insulin activity by such reagents. Our approach is part of an attempt to develop and use methods which make it unnecessary to synthesize a whole protein when a structure is required which departs only slightly from a naturally occurring one2. In the present application to insulin it resembles that of Brandenburg and Ooms3, who used Edman's phenylisothiocyanate (PITC) method4 to attack and remove tho amino terminal residues of both chains and subsequently coupled an amino-acid back in their place. In this way residues A1 and B1 had both to be replaced with the same amino-acid (glycine). In the course of the procedure, lysineB29 was (irreversibly) protected by acetylation.
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BORRÁS, F., OFFORD, R. Protected Intermediate for the Preparation of Semisynthetic Insulins. Nature 227, 716–718 (1970). https://doi.org/10.1038/227716a0
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DOI: https://doi.org/10.1038/227716a0
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