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Contribution of the B16 and B26 tyrosine residues to the biological activity of insulin

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Abstract

We report the synthesis and biological evaluation of five insulin analogues in which one or both of the B-chain tyrosine residues have been substituted. [B16 Phe]insulin and [B16 Trp]insulin display a very modest reduction in potency (c. 65%) relative to porcine insulin; [B26 Phe]insulin is less active (30–50%), and the doubly substituted [B16 Phe, B26 Phe]insulin displays still lower potency (c. 35%). The further substitution of Asp for B10 His in [B16 Phe, B26 Phe]insulin raises its activity to approximately twofold greater than natural insulin, an increase of approximately fivefold over the parent compound. We conclude that the bulk and/or aromaticity of the amino acid residue at position B16, but not its hydrogen-bonding capacity, contributes to the biological activity of the hormone. We further conclude that hydrogen-bonding capacity or special side-chain packing characteristics are required at the B26 position for insulin to display high biological activity.

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Authors and Affiliations

  1. Department of Biochemistry, Mount Sinai School of Medicine of the City University of New York, 10029-6574, New York, New York

    Shi-quan Hu, G. Thompson Burke & Panayotis G. Katsoyannis

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  1. Shi-quan Hu
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  2. G. Thompson Burke
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  3. Panayotis G. Katsoyannis
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Hu, Sq., Burke, G.T. & Katsoyannis, P.G. Contribution of the B16 and B26 tyrosine residues to the biological activity of insulin. J Protein Chem 12, 741–747 (1993). https://doi.org/10.1007/BF01024932

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  • DOI: https://doi.org/10.1007/BF01024932

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