Affiliations: [a] GrenPharma LLC, 415 South St., MS 015, Waltham, MA 02454, USA | [b] Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA, USA | [c] Department of Biology, Brandeis University, Waltham, MA, USA | [d] Department of Chemistry MS 015, Brandeis University, 415 South St., Waltham, MA 02454, USA | [e] Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA, USA
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Note: [1] Abbott Laboratories, Worcester, MA, USA.
Abstract: Extensive testing of hydrolysates of commercially available organosilanes has identified a number of bifunctional organosiloxane compounds that show potential as therapeutics for treatment of diseases characterized by amyloid deposition such as Alzheimer's disease (AD). All of these compounds protect from and/or reverse the metal-induced aggregation of amyloid Aβ(1–42) peptide in dynamic light scattering (DLS) assays in trifluoroethanol (TFE) solutions, protect from and/or reverse the metal-induced loss of α-helical structure in TFE solutions of amyloid Aβ(1–42) as measured by circular dichroism (CD), and are able to cross blood-brain barrier models at rates above background using Caco-2 and MDCK cell permeation assays. Based on these studies, we conclude that members of this class of bifunctional organosiloxanes are promising candidates for testing in treatment and/or prevention of AD and other diseases characterized by amyloid deposition.
