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Updated: Aug 19, 2026

Solid-phase Submonomer Synthesis of Peptoid Polymers and their Self-Assembly into Highly-Ordered Nanosheets
Published on: November 2, 2011
Loop-sheet polymerization: the mechanism of alpha1-antitrypsin deficiency
1Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, UK. dal16@cam.ac.uk
Abstract:
Alpha1-antitrypsin deficiency results from point mutations that distort the structure of the protein to allow a unique protein-protein interaction that we have termed loop-sheet polymerization. Polymers of Z alpha1-antitrypsin accumulate within hepatocytes to form inclusion bodies that are associated with juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein predisposes the Z alpha1-antitrypsin homozygote to emphysema. This polymerization process also occurs in variants of other members of the serine proteinase inhibitor (serpin) superfamily, antithrombin, C1-inhibitor and alpha1-antichymotrypsin in association with thrombosis, angiooedema and chronic obstructive pulmonary disease respectively, and we have recently shown that it underlies a novel inclusion body dementia. Understanding this mechanism of polymerization allows rational drug design to block the protein-protein linkage and so ameliorate the associated disease.
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