Structure-based design of peptide inhibitors of amyloid fibrillation

US8754034B2 · kind B2 · utility

Assignees

• The Regents of the University of California · US
• University of Washington · US

Inventors

• David S. Eisenberg · Los Angeles, US
• Stuart A. Sievers · San Fernando, US
• John Karanicolas · Lawrence, US
• David Baker · Ann Arbor, US

Key dates

• Filing date: Feb 8, 2010
• Grant date: Jun 17, 2014
• Expiry date: Sep 14, 2031

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2800/2821
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention provides methods for designing peptides that inhibit aggregation in target polypeptides. The candidate inhibitory peptidic compounds have an oligomeric sequence that forms energetically-favorable interactions with the amino acid sequence of the steric zipper region of the target protein, and also possess a zipper-disrupting feature that disrupt the peptide stacking at the steric zipper region. This method can be used to obtain inhibitory peptides to disrupt fibril formation involving any protein for which a steric zipper sequence can be identified. The invention also provides inhibitory peptidic compounds, which can be used in pharmaceutical compositions and methods for treating polypeptide aggregation-associated diseases or conditions.