Design and biological activity of {beta}-sheet breaker peptide conjugates
- LEPAE, Chemical Engineering Department, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal)
- Molecular Neurobiology Unit, Institute for Molecular and Cell Biology, Rua do Campo Alegre 823, 4150-180 Porto (Portugal)
- Max Planck Institute of Colloids and Interfaces, 14424 Potsdam (Germany)
The sequence LPFFD (iA{beta}{sub 5}) prevents amyloid-{beta} peptide (A{beta}) fibrillogenesis and neurotoxicity, hallmarks of Alzheimer's disease (AD), as previously demonstrated. In this study iA{beta}{sub 5} was covalently linked to poly(ethylene glycol) (PEG) and the activity of conjugates was assessed and compared to the activity of the peptide alone by in vitro studies. The conjugates were characterized by MALDI-TOF. Competition binding assays established that conjugates retained the ability to bind A{beta} with similar strength as iA{beta}{sub 5}. Transmission electron microscopy analysis showed that iA{beta}{sub 5} conjugates inhibited amyloid fibril formation, which is in agreement with binding properties observed for the conjugates towards A{beta}. The conjugates were also able to prevent amyloid-induced cell death, as evaluated by activation of caspase 3. These results demonstrated that the biological activity of iA{beta}{sub 5} is not affected by the pegylation process.
- OSTI ID:
- 21255921
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 380, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2009.01.090; PII: S0006-291X(09)00144-2; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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