3 research outputs found
Dataset for: Modulation of host cell SUMOylation facilitates efficient development of Plasmodium berghei and Toxoplasma gondii
SUMOylation is a reversible post translational modification of proteins that regulates protein stabilization, nucleocytoplasmic transport and protein-protein interactions. Several viruses and bacteria modulate host SUMOylation machinery for efficient infection. Plasmodium sporozoites are infective forms of malaria parasite that infect hepatocytes and transforms into exoerythrocytic forms (EEFs). Here we show that, during EEF development, the distribution of SUMOylated proteins in host cell nuclei was significantly reduced and expression of the SUMOylation enzymes was downregulated. Plasmodium EEFs destabilized the host cytoplasmic protein SMAD4 by inhibiting its SUMOylation. SUMO1 overexpression was detrimental to EEF growth and insufficiency of the only conjugating enzyme Ubc9/E2 promoted EEF growth. The expression of genes involved in suppression of host cell defense pathways during infection was reversed during SUMO1 overexpression, as revealed by transcriptomic analysis. The inhibition of host cell SUMOylation was also observed in Toxoplasma. We provide a hitherto unknown mechanism of regulating host gene expression through altering host SUMOylation by Apicomplexan parasites
Supramolecular Organo/hydrogel-Fabricated Long Alkyl Chain α‑Amidoamides as a Smart Soft Material for pH-Responsive Curcumin Release
Low-molecular-mass gelators, due to their excellent biocompatibility,
low toxicological profile, innate biodegradability and ease of fabrication
have garnered significant interest as they self-assemble through non-covalent
interactions. In this study, we have designed and synthesized a series
of six α-amidoamides by varying the hydrophobic alkyl chain
length (C12–C22), which were well characterized
using different spectral techniques. These α-amidoamides formed
self-assembled aggregates in a DMSO/water solvent system affording
organo/hydrogels at 0.66% w/v, which is the minimum gelation concentration
(MGC) making them as remarkable supergelators. The various functionalities
present in these gelators such as amides and alkyl chain length pave
the way toward excellent gelation mechanism through hydrogen bonding
and van der Waals interaction as evidenced from FTIR spectroscopy.
Notably, as the chain length increased, organo/hydrogels became more
thermally stable. Rheological results showed that the stability and
strength of these gelators were considerably impacted by variations
in chain length. The SEM morphology revealed dense sheet architectures
of the organo/hydrogel samples. Organo/hydrogels have a significant
impact on the advancement of innovative drug delivery systems that
respond to various stimuli, ushering in a new era in pharmaceutical
technology. Inspired by this, we encapsulated curcumin, a chemopreventive
medication, into the gel core and further released via gel-to-sol transition induced by pH variation at 37 °C, without
any alteration in structure–activity relationship. The drug
release behavior was observed by UV–vis spectroscopy. Moreover,
cell viability and cell invasion experiments demonstrate that the
gel formulations exhibit high biocompatibility and low cytotoxicity.
Among the tested formulations, 5e+Cur exhibited remarkable
efficacy in controlling A549 cell migration, suggesting significant
potential for applications in the pharmaceutical industry
Design, synthesis, and biological evaluation of multiple targeting antimalarials
International audienceMalaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule, RYL-581, which binds to multiple protein binding sites of P. falciparum simultaneousl