The sequence LPFFD (iA beta(5)) prevents amyloid-beta peptide (A beta) fibrillogenesis and neurotoxicity, hallmarks of Alzheimer's disease (AD), as previously demonstrated. In this Study iA beta 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(5). Transmission electron microscopy analysis showed that iA beta(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(5) is not affected by the pegylation Process. (C) 2009 Elsevier Inc. All rights reserved.