Incorporating a β-hairpin sequence motif to increase intracellular stability of a peptide-based PROTAC.

ABSTRACT: Proteolysis targeting chimeras (PROTACs) have emerged as a new class of therapeutics that utilize the ubiquitin-proteasome system (UPS) to facilitate proteasomal degradation of "undruggable" targets. Peptide-based PROTACs contain three essential components: a binding motif for the target protein, a short amino acid sequence recognized by an E3 ligase called a degron, and a cell penetrating peptide to facilitate uptake into intact cells. While peptide-based PROTACs have been shown to successfully degrade numerous targets, they have often been found to exhibit low cell permeability and high protease susceptibility. Prior work identified peptides containing a β-hairpin sequence motif that function not only as protecting elements, but also as CPPs and degrons. The goal of this study was to inv

SUBMITTER: Hymel HC 

PROVIDER: S-EPMC10455042 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature