Disruptin, a cell-penetrating peptide degrader of EGFR: Cell-Penetrating Peptide in Cancer Therapy.

ABSTRACT: Disruptin is a cell-permeable decoy peptide designed to destabilize activated EGFR, both by inhibiting Hsp90 chaperoning and dissociating the active asymmetric EGFR dimer, which leads to an increase in engagement of activated EGFR with the proteolytic degradation machinery and subsequent loss from the cells. Disruptin is an N-terminally biotinylated nonadecapeptide, with 8 amino acids from the αC-helix-β4 sheet loop of EGFR (S⁷⁶⁷-C⁷⁷⁴) fused to a TAT undecapeptide. The S⁷⁶⁷-R⁷⁷⁵ loop is at the interface with juxtamembrane domains in the active EGFR dimers and is a binding site for Hsp90. Cellular studies in EGFR-activated tumor cells demonstrated that Disruptin causes the disappearance of EGFR protein from cells over a few hours, a growth inhibit

SUBMITTER: Mehta RK 

PROVIDER: S-EPMC8187233 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature