Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes

Tumorimmunolog

Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice

N-acylethanolamines (NAEs), which include the endocannabinoid anandamide, represent an important family of signaling lipids in the brain. The lack of chemical probes that modulate NAE biosynthesis in living systems hamper the understanding of the biological role of these lipids. Using a high-throughput screen, chemical proteomics and targeted lipidomics, we report here the discovery and characterization of LEI-401 as a CNS-active N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor. LEI-401 reduced NAE levels in neuroblastoma cells and in the brain of freely moving mice, but not in NAPE-PLD KO cells and mice, respectively. LEI-401 activated the hypothalamus–pituitary–adrenal axis and impaired fear extinction, thereby emulating the effect of a cannabinoid CB1 receptor antagonist, which could be reversed by a fatty acid amide hydrolase inhibitor. Our findings highlight the distinctive role of NAPE-PLD in NAE biosynthesis in the brain and suggest the presence of an endogenous NAE tone controlling emotional behavior.NWOMicrobial Biotechnolog

Bioorthogonal deprotection strategy to study T-cell activation and cross-presentation

Cytotoxic T-cells (CTLs) are involved in the clearance of viruses and killing of tumor cells. The capacity of these killer cells to clear viruses and kill tumor cells can be harbored by the creation of vaccines. Improving understanding of T-cell activation and the possibility to understand, influence or even have control over this process might lead to better anti-cancer vaccines. Chemical tools can be a good addition to fill in the gaps of knowledge about T-cell activation.Bio-organic Synthesi