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Replacement of ProB28 by pipecolic acid protects insulin against fibrillation and slows hexamer dissociation

Author:
Fang, Katharine Y., Lieblich, Seth A., Tirrell, David A.
Source:
Journal of polymer science 2019 v.57 no.3 pp. 264-267
ISSN:
0887-624X
Subject:
dissociation, engineering, insulin, mutagenesis, pipecolic acid, polymers, proline, therapeutics
Abstract:
Non‐canonical amino acid mutagenesis was used to examine the biophysical consequences of changing ring size and structure at the single proline site in insulin. Addition of a methylene spacer to the prolyl ring (by replacement of proline by pipecolic acid at position B28) led to an increase in stability and a decrease in the rate of hexamer dissociation. The results of this work illustrate the power of non‐canonical amino acid mutagenesis in the engineering of macromolecular aggregation and protein therapeutics.
Agid:
6268034