Development of a peptide-based inducer of nuclear receptors degradation

作者：Demizu Yosuke^*; Ohoka Nobumichi; Nagakubo Takaya; Yamashita Hiroko; Misawa Takashi; Okuhira Keiichiro; Naito Mikihiko; Kurihara Masaaki^*

来源：Bioorganic & Medicinal Chemistry Letters, 2016, 26(11): 2655-2658.

DOI：10.1016/j.bmcl.2016.04.013

• Nuclear receptors
• Helical peptide
• Protein-protein interaction
• Protein knockdown

A peptide-based protein knockdown system for inducing nuclear receptors degradation via the ubiquitin-proteasome system was developed. Specifically, the designed molecules were composed of two biologically active scaffolds: a peptide that binds to the estrogen receptor alpha (ER alpha) surface and an MV1 molecule that binds to cellular inhibitors of apoptosis proteins (IAP: cIAP1/cIAP2/XIAP) to induce ubiquitylation of the ER alpha. The hybrid peptides induced IAP-mediated ubiquitylation followed by proteasomal degradation of the ER alpha. Those peptides were also applicable for inducing androgen receptor (AR) degradation.

• 出版日期2016-6-1