Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
Bioorg Med Chem. 2024 Mar 15;102:117672. doi: 10.1016/j.bmc.2024.117672. Epub 2024 Mar 2.
Small molecules that chemically induce proximity between two proteins have been widely used to precisely modulate protein levels, stability, and activity. Recently, several studies developed novel strategies that employ heterobifunctional molecules that co-opt shuttling proteins to control the spatial localization of a target protein, unlocking new potential within this domain. Together, these studies lay the groundwork for novel targeted protein relocalization modalities that can rewire the protein circuitry and interactome to influence biological outcomes.
小分子可以通过化学方法诱导两个蛋白质之间的接近,从而被广泛用于精确调节蛋白质的水平、稳定性和活性。最近,有几项研究开发了新的策略,利用异双功能分子来利用穿梭蛋白来控制靶蛋白的空间定位,从而在这个领域中开辟了新的潜力。这些研究为新型靶向蛋白重定位模式奠定了基础,这种模式可以重新构建蛋白质电路和相互作用组,从而影响生物结果。