Department of Chemistry, Tsinghua University, Key Lab of Bioorganic Phosphorus Chemistry and Chemical Biology, Beijing, 100084, P. R. China.
Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada.
Chembiochem. 2020 Apr 17;21(8):1150-1154. doi: 10.1002/cbic.201900591. Epub 2020 Jan 20.
The activation of toll-like receptors (TLRs) plays important roles in the immune response. The ability to control the activities of TLRs could be usable as a switch for immune response. Here we have rationally designed and synthesized a photoswitchable Pam CSK derivative-P10-to control the activation of TLR1/2. The ground-state trans-P10 was able to stimulate and activate antigen-presenting cells (APCs) by promoting TLR1/2 heterodimerization. However, cis-P10, derived from UV irradiation of trans-P10, reduced the activities of APCs by impeding the TLR1/2 heterodimerization. In the absence of UV radiation, the cis-P10 slowly returned to its ground trans state, restoring the activities of the APCs stimulation. Our results indicated that optical control of TLR1/2 heterodimerization mediated by the photoswitchable P10 offers the potential to regulate immune activation and inflammation.
Toll-like 受体 (TLRs) 的激活在免疫反应中起着重要作用。控制 TLRs 活性的能力可用作免疫反应的开关。在这里，我们合理设计并合成了一种光可切换的 Pam CSK 衍生物-P10-来控制 TLR1/2 的激活。基态反式-P10 通过促进 TLR1/2 异二聚化来刺激和激活抗原呈递细胞 (APC)。然而，顺式-P10 是由反式-P10 的紫外线照射产生的，通过阻碍 TLR1/2 异二聚化来降低 APC 的活性。在没有紫外线辐射的情况下，顺式-P10 会缓慢恢复到其基态反式状态，恢复 APC 刺激的活性。我们的结果表明，光可切换的 P10 介导的 TLR1/2 异二聚化的光学控制为调节免疫激活和炎症提供了潜力。
