Theme 2
The initial phase of this project has focused on synthesising a first generation of RNA-binding protein degraders to reproduce and validate results previously reported.1,2 These degraders consist of three components: a von Hippel-Lindau (VHL) E3 ligase recruiter, a linker, and an oligonucleotide (ON) designed to bind the target RNA-binding protein, Lin28A.
To date, eight degrader constructs have been synthesised, including four active degraders targeting Lin28A and four negative controls. These constructs combine different VHL recruiters, oligonucleotide lengths, and conjugation chemistries to assess the contribution of each component to degrader activity.
1 A. Ghidini, A. Cléry, F. Halloy, F. H. T. Allain, J. Hall Angew. Chem. Int. Ed. 2021, 60, 3163 – 3169. 2 Jianfei Xu, Xingxing Liang, Zhaopeng Yan, Yuejie Zhu, Jing Wang, Qian Wang, Zhenjun Yang, and Xinjing Tang J. Med. Chem. 2026 69, 4567-4578.