Targeted Biomolecule Regulation Platform: A Split-and-Mix PROTAC Approach

Authors:
Publisher website
Google Scholar
Abstract
The development of bifunction al molecules, which can enable targeted RNA degradation, targeted protein acetylation, or targeted protein degradation, remains a time-consuming process that requires tedious optimization. We propose a split-and-mix nanoplatform that serves as a self-adjustable platform capable of facile screening, programmable ligand ratios, self-optimized biomolecule spatial recognition, and multifunctional applications. Herein, we demonstrate the potential of our proposed nanoplatform by showcasing proteolysis-targeting chimeras (PROTACs), namely, split-and-mix PROTAC (SM-PROTAC). We highlight the scope of our platform through the targeted disruption of intracellular therapeutic targets involving ERα, CDK4/6, AR, MEK1/2, BRD2/4, BCR-ABL, etc. These studies confirm the effectiveness and universality of the SM-PROTAC platform for proximity-induced applications. This platform is programmable, with significant potential applications to biomolecule regulation, including the fields of epigenetics, gene editing, and biomolecule modification regulation.
Funding Information
  • Peking University
  • Ministry of Science and Technology of the People's Republic of China (2021YFA0910803, 2021YFC2103900)
  • Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20180507181527112, JCYJ20200109140406047, RCJC20200714114433053)
  • National Natural Science Foundation of China (21977010)
  • Natural Science Foundation of Guangdong Province (2020A1515011544, 2022A1515010996)
  • Shenzhen-Hong Kong Institute of Brain Science (2019SHIBS0004)
  • National Center for Biopharmaceutical Technology Innovation (NCTIB2022HS01017)
  • Shenzhen Key Medical Discipline Construction Fund (SZXK060)
  • Shenzhen Fundamental Research Institutions (2019SHIBS0004)

This publication has 31 references indexed in Scilit: