Proteolysis Targeting Chimera (PROTAC) is a heterobifunctional small molecule with three chemical elements: a ligand binding to a target, a ligand binding to E3 ligase and a linker for conjugating these two ligands. PROTAC leads to ubiquitin-dependent proteolysis of the target. As vital part in PROTAC molecules, E3 ligase ligand is required to degrade the specificity protein targets. The successfully applied E3 ubiquitin ligases are among cell inhibitor of apoptosis protein (cIAP), cereblon (CRBN), murine double minute 2 (MDM2) and Von-Hippel-Lindau (VHL). Different from traditional small molecule ligands, the peptide PROTAC modality as a novel strategy for targeted protein ubiquitination have been attracted the attention of scientists.
Unlike small molecule PROTAC, peptide PROTAC with advantages of high specificity, and low toxicity, which provides a promising application for PROTAC design. With the development of structural biology, it is convenient to obtain the peptides with high affinity to target protein epitopes and avoid the restriction of shallow binding pockets between protein and traditional small compounds.
Profacgen provides the peptide design services based on the crystal structure of endogenous complex of target protein and the protein-protein interaction motif. With the sequence optimization and mutation, peptide with high stability and good cell permeability will be designed and synthesized.
Figure 1. The schematic diagram of peptide PROTAC
PROTAC has successfully applied to variety of target classes for offering greater degradation selectivity. The specificity and affinity of ligands for target proteins are critical for PROTAC to potentially treat diseases.
Figure 1. Key elements in peptide design.
Profacgen is fully competent to provide various peptides design for E3 ligase or target protein service. Please feel free to contact us for a detailed quotation.
1. Gao H, Sun X, Rao Y. (2020). PROTAC technology: opportunities and challenges. ACS Medicinal Chemistry Letters, 11(3), 237–240. doi:10.1021/acsmedchemlett.9b00597
2. Jinmei Jin, Ye Wu et al. The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination. Theranostics 2020; 10(22):10141-10153. doi:10.7150/thno.46985