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Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2.

Häußler, Daniela Mangold, Martin Furtmann, Norbert Braune, Annett Blaut, Michael Bajorath, Jürgen Stirnberg, Marit Gütschow, Michael

Published in Chemistry (Weinheim an der Bergstrasse, Germany)

Matriptase-2, a type II transmembrane serine protease, plays a key role in human iron homeostasis. Inhibition of matriptase-2 is considered as an attractive strategy for the treatment of iron-overload diseases, such as hemochromatosis and β-thalassemia. In the present study, synthetic routes to nine dipeptidomimetic inactivators were developed. Fiv...

Introduction of d-Glutamate at a Critical Residue of Aβ42 Stabilizes a Prefibrillary Aggregate with Enhanced Toxicity. PDF available through Get Fulltext Research

Warner, Christopher J A Dutta, Subrata Foley, Alejandro R Raskatov, Jevgenij A

Published in Chemistry (Weinheim an der Bergstrasse, Germany)

The amyloid beta peptide 42 (Aβ42) is an aggregation-prone peptide that plays a pivotal role in Alzheimer's disease. We report that a subtle perturbation to the peptide through a single chirality change at glutamate 22 leads to a pronounced delay in the β-sheet adoption of the peptide. This was accompanied by an attenuated propensity of the peptide...

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