2 research outputs found
Development of a Photo-Cross-Linkable Diaminoquinazoline Inhibitor for Target Identification in <i>Plasmodium falciparum</i>
Diaminoquinazolines
represent a privileged scaffold for antimalarial discovery, including
use as putative <i>Plasmodium</i> histone lysine methyltransferase
inhibitors. Despite this, robust evidence for their molecular targets
is lacking. Here we report the design and development of a small-molecule
photo-cross-linkable probe to investigate the targets of our diaminoquinazoline
series. We demonstrate the effectiveness of our designed probe for
photoaffinity labeling of <i>Plasmodium</i> lysates and
identify similarities between the target profiles of the probe and
the representative diaminoquinazoline BIX-01294.
Initial pull-down proteomics experiments identified 104 proteins from
different classes, many of which are essential, highlighting the suitability
of the developed probe as a valuable tool for target identification
in <i>Plasmodium falciparum</i>
Development of a Fluorescent Bodipy Probe for Visualization of the Serotonin 5‑HT<sub>1A</sub> Receptor in Native Cells of the Immune System
Serotonin
(5-HT) modulates key aspects of the immune system. However,
its precise function and the receptors involved in the observed effects
have remained elusive. Among the different serotonin receptors, 5-HT<sub>1A</sub> plays an important role in the immune system given its presence
in cells involved in both the innate and adaptive immune responses,
but its actual levels of expression under different conditions have
not been comprehensively studied due to the lack of suitable tools.
To further clarify the role of 5-HT<sub>1A</sub> receptor in the immune
system, we have developed a fluorescent small molecule probe that
enables the direct study of the receptor levels in native cells. This
probe allows direct profiling of the receptor expression in immune
cells using flow cytometry. Our results show that important subsets
of immune cells including human monocytes and dendritic cells express
functional 5-HT<sub>1A</sub> and that its activation is associated
with anti-inflammatory signaling. Furthermore, application of the
probe to the experimental autoimmune encephalomyelitis model of multiple
sclerosis demonstrates its potential to detect the specific overexpression
of the 5-HT<sub>1A</sub> receptor in CD4+ T cells. Accordingly, the
probe reported herein represents a useful tool whose use can be extended
to study the levels of 5-HT<sub>1A</sub> receptor in ex vivo samples
of different immune system conditions