HYDROCARBON-STAPLED POLYPEPTIDES FOR ENHANCEMENT OF ENDOSOME-LYSOSOMAL DEGRADATION
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Jan 4, 2018
app pub date -
Jun 29, 2017
filing date -
Jun 29, 2016
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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.
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