Effects of Insulin Concentration and Self-Association on the Partitioning of Its A-21 Cyclic Anhydride Intermediate to Desamido Insulin and Covalent Dimer

@article{Darrington1995EffectsOI,
  title={Effects of Insulin Concentration and Self-Association on the Partitioning of Its A-21 Cyclic Anhydride Intermediate to Desamido Insulin and Covalent Dimer},
  author={Richard T. Darrington and Bradley D. Anderson},
  journal={Pharmaceutical Research},
  year={1995},
  volume={12},
  pages={1077-1084}
}
Purpose. In the pH range 2–5, human insulin degrades via deamidation at the A-21 asn and covalent dimerization. Both products form via a common cyclic anhydride intermediate, a product of intramolecular nucleophilic attack by the A-21 carboxyl terminus. This study examines the influence of [insulin] and self-association on the partitioning of the intermediate to products. Methods. Insulin self-association was characterized (pH 2–4) by concentration difference spectroscopy. Deamidation rates (pH… CONTINUE READING

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