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Halogenation of the N-Terminus Tyrosine 10 Promotes Supramolecular Stabilization of the Amyloid-β Sequence 7–12 |
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| Authors: | Dr Daniele Maiolo Dr Andrea Pizzi Dr Alessandro Gori Dr Lara Gazzera Dr Nicola Demitri Dr Alessandro Genoni Dr Fulvio Baggi Dr Fabio Moda Prof Dr Giancarlo Terraneo Prof Dr Francesca Baldelli Bombelli Prof Dr Pierangelo Metrangolo Prof Dr Giuseppe Resnati |
| Institution: | 1. Dept. Chem., Mater., and Chem. Eng. “Giulio Natta”, Politecnico di Milano, Via L. Mancinelli 7, 20131 Milano, Italy;2. Istituto di Scienze e Tecnologie Chimiche, National Research Council of Italy, Via M. Bianco 9, 20131 Milano, Italy;3. Elettra – Sincrotrone Trieste, S.S. 14 Km 163.5 in Area Science Park, 34149 Basovizza – Trieste, Italy;4. Laboratoire de Physique et Chimie Théoriques, Université de Lorraine and CNRS UMR CNRS 7019, 1 Boulevard Arago, 57078 Metz, France;5. Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Via G. Celoria 11, 20133 Milan, Italy |
| Abstract: | Here, we demonstrate that introduction of halogen atoms at the tyrosine 10 phenol ring of the DSGYEV sequence derived from the flexible amyloid-β N-terminus, promotes its self-assembly in the solid state. In particular, we report the crystal structures of two halogen-modified sequences, which we found to be stabilized in the solid state by halogen-mediated interactions. The structural study is corroborated by Non-Covalent Interaction (NCI) analysis. Our results prove that selective halogenation of an amino acid enhances the supramolecular organization of otherwise unstructured biologically-relevant sequences. This method may develop as a general strategy for stabilizing highly polymorphic peptide regions. |
| Keywords: | halogen bonding crystal engineering supramolecular bromine peptide |