Bifunctional stapled polypeptides and uses thereof

US9163330B2 · kind B2 · utility

Assignee

• President and Fellows of Harvard College · US

Inventors

• Gregory L. Verdine · Boston, US
• Tom N. Grossmann · Dortmund, DE
• Raymond E. Moellering · Chicago, US
• Tsung-Han Johannes Yeh · Brookline, US
• Yue Rebecca Yue Liang · Cambridge, US
• Youbean Oak · Cambridge, US

Key dates

• Filing date: Jul 13, 2010
• Grant date: Oct 20, 2015
• Expiry date: Apr 24, 2031

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/01
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention relates to bifunctional stapled or stitched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stitched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stitched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stitched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Uses of the inventive bifunctional stapled or stitched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.