PuSH - Publikationsserver des Helmholtz Zentrums München

Andreetto, E.* ; Malideli, E.* ; Yan, L.M.* ; Kracklauer, M.* ; Farbiarz, K.* ; Tatarek-Nossol, M.* ; Rammes, G.* ; Prade, E. ; Neumüller, T.* ; Caporale, A.* ; Spanopoulou, A.* ; Bakou, M.* ; Reif, B. ; Kapurniotu, A.*

A hot-segment-based approach for the design of cross-amyloid interaction surface mimics as inhibitors of amyloid self-assembly.

Angew. Chem.-Int. Edit. 54, 13095-13100 (2015)
Verlagsversion DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The design of inhibitors of protein-protein interactions mediating amyloid self-assembly is a major challenge mainly due to the dynamic nature of the involved structures and interfaces. Interactions of amyloidogenic polypeptides with other proteins are important modulators of self-assembly. Here we present a hot-segment-linking approach to design a series of mimics of the IAPP cross-amyloid interaction surface with Aβ (ISMs) as nanomolar inhibitors of amyloidogenesis and cytotoxicity of Aβ, IAPP, or both polypeptides. The nature of the linker determines ISM structure and inhibitory function including both potency and target selectivity. Importantly, ISMs effectively suppress both self- and cross-seeded IAPP self-assembly. Our results provide a novel class of highly potent peptide leads for targeting protein aggregation in Alzheimer's disease, type 2 diabetes, or both diseases and a chemical approach to inhibit amyloid self-assembly and pathogenic interactions of other proteins as well.
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Alzheimer’s Disease ; Amyloid Inhibitors ; Islet Amyloid Polypeptide ; Protein-protein Interactions ; β-amyloid Peptide
ISSN (print) / ISBN 1433-7851
e-ISSN 1521-3773
Quellenangaben Band: 54, Heft: 44, Seiten: 13095-13100 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Weinheim
Begutachtungsstatus Peer reviewed