HBS-α-helicomimics

HBS-α-helicomimics are a novel class of chemically engineered, α-helix mimicking polypeptides designed to target TMPRSS2-ERG fusion-driven prostate cancer. Developed by researchers at the Indian Institute of Technology Kanpur and the Indian Institute of Science Bangalore, these helicomimics utilize a Hydrogen Bond Surrogate (HBS) approach to stabilize the α-helical conformation, incorporating non-biodegradable N-terminal HBS-turns and a thermally stable backbone to enhance in vivo stability and DNA affinity. The mechanism of action involves specific binding to the ETS consensus DNA motif, which directly blocks the interaction between the ERG transcription factor and its target DNA sequences. This disruption inhibits ERG-mediated transcriptional activity and its oncogenic interactions with cofactors such as the androgen receptor (AR), leading to reduced proliferation, migration, and invasion in ERG-positive prostate cancer cells.