Hydrocarbon-stapled polypeptides for enhancement of endosome-lysosomal degradation

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.