Hydrocarbon-stapled polypeptides for enhancement of endosome-lysosomal degradation
OwnerYanxiang ZHAO, Shuai WU +4inventors
InventorsYanxiang ZHAO, Shuai WU, Wenchao YANG, Yunjiao HE, Xiaohua LI, Xianxiu QIU
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Abstract
The present invention relates to a Beclin1-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 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.
Claims16
A hydrocarbon-stapled polypeptide designed to target a polypeptide comprising amino acid residues 231-245 of rat Beclin 1 (SEQ ID No.:
- 15), or amino acids 233-247 of human Beclin 1 (SEQ ID No.:
- 16), said hydrocarbon-stapled polypeptide comprises an amino acid sequence that is at least 85% identical to amino acid residues 191-205 of rat Beclin 1 (SEQ ID No.:
- 17), or amino acids 193-207 of human Beclin 1 (SEQ ID No.:
- 18).
Dependencies are inferred from the claim text.