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Type: Journal article
Title: Total chemical synthesis of an intra-A-chain cystathionine human insulin analogue with enhanced thermal stability
Author: Karas, J.
Patil, N.
Tailhades, J.
Sani, M.
Scanlon, D.
Forbes, B.
Gardiner, J.
Separovic, F.
Wade, J.
Hossain, M.
Citation: Angewandte Chemie - International Edition, 2016; 55(47):14743-14747
Publisher: Wiley
Issue Date: 2016
ISSN: 1433-7851
Statement of
John A. Karas, Nitin A. Patil, Julien Tailhades, Marc-Antoine Sani, Denis B. Scanlon, Briony E. Forbes, James Gardiner, Frances Separovic, John D. Wade, and Mohammed Akhter Hossain
Abstract: Despite recent advances in the treatment of diabetes mellitus, storage of insulin formulations at 48C is still necessary to minimize chemical degradation. This is problematic in tropical regions where reliable refrigeration is not ubiquitous. Some degradation byproducts are caused by disulfide shuffling of cystine that leads to covalently bonded oligomers. Consequently we examined the utility of the non-reducible cystine isostere, cystathionine, within the A-chain. Reported herein is an efficient method for forming this mimic using simple monomeric building blocks. The intra-A-chain cystathionine insulin analogue was obtained in good overall yield, chemically characterized and demonstrated to possess native binding affinity for the insulin receptor isoform B. It was also shown to possess significantly enhanced thermal stability indicating potential application to next-generation insulin analogues.
Keywords: Cystathionine; cysteine; diabetes mellitus; insulin; solid-phase peptide synthesis
Rights: © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
RMID: 0030057129
DOI: 10.1002/anie.201607101
Grant ID:
Appears in Collections:Medical Sciences publications

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