Conformational analysis of peptides derived from the BRI gene

Article type: Research Article

Authors: Lelyveld, Victor | El‐Agnaf, Omar^; | Siligardi, Giuliano | Hussain, Rohana | Haris, Parvez I. | Lee, Maria | Austen, Brian^;

Affiliations: Neurodegeneration Unit, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK | Department of Pharmacy, King's College, Franklin‐Wilkins Building, 150 Stamford Street, London SE1 8WA, UK | Department of Biological Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK

Note: [] Present address: Department of Biological Sciences, University of Lancaster, Lancaster LA1 4YQ, UK.

Note: [] Corresponding author: Tel.: +44 208 725 5651; Fax: +44 208 725 3594; E‐mail: [email protected].

Abstract: The 34‐residue peptides (ABri and ADan) derived from the 3′ end of the gene BRI which is mutated in British and Danish families with dementia, have been synthesized, with and without the predicted intramolecular disulphides. CD measurements show that the oxidised and reduced forms have tendencies to adopt β‐structure at neutral pH with prolonged time of incubation. The shift to β‐structure is accompanied by oligomer formation. The neurotoxic properties of these oligomers in vitro may explain the cognitive decline seen in the patients. Structural analyses will be useful in the design of therapeutic drugs.

Journal: Spectroscopy, vol. 15, no. 3-4, pp. 129-139, 2001