Hydrocarbon-stapled polypeptides for enhancement of endosome-lysosomal degradation

US10618939B2 · kind B2 · utility

Assignee

• The Hong Kong Polytechnic University · CN

Inventors

• Yanxiang ZHAO · New York, US
• Shuai Wu · Waltham, US
• Wenchao Yang · 红钢城街道, CN
• Yunjiao HE · Hong Kong, CN
• Xiaohua Li · Shanghai, CN
• Xianxiu QIU · Hong Kong, CN

Key dates

• Filing date: Mar 14, 2018
• Grant date: Apr 14, 2020
• Expiry date: Mar 23, 2038

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P35/00
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

The present invention relates to a Beclin 1-UVRAG complex structure which reveals a tightly packed coiled coil assembly with Beclin 1 and UVRAG residues complementing each other to form a stable dimeric complex. This potent physical interaction is critical for UVRAG-dependent EGFR degradation but less critical for autophagy. Targeting the Beclin 1 coiled coil domain with rationally designed stapled peptides leads to enhanced autophagy activity and EGFR degradation in non-small cell lung cancer (NSCLC) cell lines, suggesting translational value for these compounds.