公开(公告)号：US20240190920A1

公开(公告)日：2024-06-13

申请号：US18550862

申请日：2022-05-11

申请人： Shenzhen Research Institute of the Hong Kong Polytechnic University ,  FUDAN UNIVERSITY

发明人： Yanxiang ZHAO ,  Xianxiu QIU ,  Xiaozhe ZHANG ,  Na LI ,  Renxiao WANG

IPC分类号： C07K7/08

CPC分类号： C07K7/08

摘要： A Beclin 1-targeting stapled peptide and a pharmaceutical composition. The stapled peptide includes an amino acid sequence at least 66.7% identical to amino acid residues 191-205 of Beclin 1, an amino acid residue E195 and an amino acid residue N202 in the stapled peptide are connected by a hydrocarbon staple to stabilize the α-helical structure of the stapled peptide. The hydrocarbon staple is located at a position in the stapled peptide closer to the Beclin1 coiled coil domain-stapled peptide binding interface, which can enhance the binding affinity of the stapled peptide to Beclin 1 by 10-30 fold. Compared to other autophagy inducers like rapamycin and Tat-Beclin 1 peptide, the optimized stapled peptide shows the unique profile of not only inducing autophagy but also significantly enhancing the endolysosomal degradation of cell surface oncogenic receptors EGFR and HER2 in HER2-positive cancer cells.