Ontology highlight
ABSTRACT:
SUBMITTER: Jenson JM
PROVIDER: S-EPMC5464773 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Jenson Justin M JM Ryan Jeremy A JA Grant Robert A RA Letai Anthony A Keating Amy E AE
eLife 20170608
Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membran ...[more]