Medical imaging has relied on ultrasound (US) as an exploratory method for decades. Nonetheless, in cell biology, the numerous US applications are mainly in the research and development phase. In this review, we report the main effects on human or mammal cells of US induced by bulk or surface acoustic waves (SAW). At low frequencies, bulk US can le...
The development of peptide inhibitors against intracellular targets depends upon the dual challenge of achieving a high affinity and specificity for the target and maintaining cellular permeability for biological activity. Previous efforts to develop bicyclic peptides targeted to the Grb7 signalling protein implicated in HER2+ve cancer progression ...
β-Amyloid (Aβ) is a hallmark peptide of Alzheimer’s disease (AD). Herein, we explored the mechanism underlying the cytotoxicity of this peptide. Double treatment with oligomeric 42-amino-acid Aβ (Aβ42) species, which are more cytotoxic than other conformers such as monomers and fibrils, resulted in increased cytotoxicity. Under this treatment condi...
The cell membrane permeability of a cell type to water (Lp) and cryoprotective agents (Ps), is the key factor that determines the optimal cooling and mass transportation during cryopreservation. The human lung adenocarcinoma cell line, CL1, has been widely used to study the invasive capabilities or drug resistance of lung cancer cells. Therefore, p...
Cysteine cathepsin proteases are found under normal conditions in the lysosomal compartments of cells, where they play pivotal roles in a variety of cellular processes such as protein and lipid metabolism, autophagy, antigen presentation, and cell growth and proliferation. As a consequence, aberrant localization and activity contribute to several p...
Published in SLAS discovery : advancing life sciences R & D
The recent renascence of phenotypic drug discovery (PDD) is catalyzed by its ability to identify first-in-class drugs and deliver results when the exact molecular mechanism is partially obscure. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition with a high mortality rate that has increased in frequency due to the CO...
A recently discovered bisubstrate inhibitor of Nicotinamide N-methyltransferase (NNMT) was found to be highly potent in biochemical assays with a single digit nanomolar IC50 value but lacking in cellular activity. We, here, report a prodrug strategy designed to translate the observed potent biochemical inhibitory activity of this inhibitor into str...
Published in Chemmedchem
Without a trace : Fluorescent amino acids ClAc−4CNW, ClAc−AzAla were incorporated into in vitro translated macrocyclic peptides by genetic code reprogramming. The minimally perturbing dyes were found to be good tools for tracking peptide penetration into cells by fluorescence imaging and flow cytometry.
The major obstacle in applying peptides to intracellular targets is their low inherent cell permeability. Standard approaches to attach a fluorophore (e.g. FITC, TAMRA) can change the physicochemical properties of the parent peptide and influence their ability to penetrate and localize in cells. We report a label-free strategy for evaluating the ce...
SGLT-2i’s exert direct anti-inflammatory and anti-oxidative effects on resting endothelial cells. However, endothelial cells are constantly exposed to mechanical forces such as cyclic stretch. Enhanced stretch increases the production of reactive oxygen species (ROS) and thereby impairs endothelial barrier function. We hypothesized that the SGLT-2i...
