Potent Inhibition of HIF1α and p300 Interaction by a Constrained Peptide Derived from CITED2

Disrupting the interaction between HIF1α and p300 is a promising
strategy to modulate the hypoxia response of tumor cells. Herein,
we designed a constrained peptide inhibitor derived from the CITED2/p300
complex to disturb the HIF1α/p300 interaction. Through truncation/mutation
screening and a terminal aspartic acid-stabilized strategy, a constrained
peptide was constructed with outstanding biochemical/biophysical properties,
especially in binding affinity, cell penetration, and serum stability.
To date, our study was the first one to showcase that stabilized peptides
derived from CITED2 using helix-stabilizing methods acted as a promising
candidate for modulating hypoxia-inducible signaling.