Scheme 1. Utilization of Double-Stapled Peptide Chemistry in the Development of the Peptide PROTAC Drug Has Resulted in the Acquisition of Sophisticated Structural Features, Including the Simultaneous Incorporation of α-Helix and β-Sheet Motifs.

These structural modifications contribute to the notable enhancement of stability and improved membrane penetration capabilities of the stapled peptide PROTAC drug. Significantly, the stapled peptide PROTAC drugs have demonstrated the capacity to induce the degradation of both AR and AR-V7 in prostate cancer cells. Also, the stapled peptide PROTAC drugs effectively impede the progression of prostate cancer in vitro and in vivo. These findings highlight the potential of stapled peptide PROTAC drugs as a promising therapeutic strategy for the treatment of prostate cancer, offering a new avenue for combating this disease.