Majumder, J. | bioRxiv Science

bioRxiv2020

Amino-alcohol Bio-conjugate of Naproxen Exhibits Anti-inflammatory Activity through NF-κB Signaling Pathway

Naproxen sodium (Ns) is a well-known synthetic compound used vastly as a nonsteroidal anti-inflammatory drug (NSAID). Previously, we demonstrated that the hydrogels, made of Ns bio-conjugate (NBC), either with amino alcohol (NBC-1 and 2) or amino acid (NBC-3 and 4), displayed anti-inflammatory properties better than Ns, but the effectiveness was not well explored. Here, we investigated that NBC-2, conjugated with {gamma}-amino alcohol, significantly reduces the expression of pro-inflammatory proteins; such as inducible nitric oxide synthase (iNOS) and cyclooxygenase isoform-2 (COX-2), and the production of pro-inflammatory mediator nitric oxide (NO) in lipopolysaccharide and interferon-{gamma} (LPS/IFN-{gamma}) treated mouse macrophage RAW 264.7 cells, compared with bio-conjugation of {beta}-amino alcohol (NBC-1) or {beta}-amino acid (NBC-3) or -amino acid NBC (NBC-4). NBC-2 decreases the nuclear localization of transcription factors NF-{kappa}B by stabilizing its cytoplasmic functional inhibitor I{kappa}B. Moreover, NBC-2 also displays selective inhibitory effect towards COX-1 enzyme activity as determined by enzymatic assay and in silico molecular docking analysis. Thus, we suggest that NBC-2 may be used as a self-delivery anti-inflammatory drug as compared with other NBCs. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/901223v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1ab255borg.highwire.dtl.DTLVardef@121aa6eorg.highwire.dtl.DTLVardef@13c4b86org.highwire.dtl.DTLVardef@1827207_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2018

Stable and Reversible Functionalization of the Native Phosphate Groups on Live Cells

Surface modification of live cells has important biomedical and therapeutic applications. Current methods to label cells require artificial cell surface engineering (via metabolic, docking or anchoring methods) before conjugative chemistries, which is not always trivial to accomplish and/or not appropriate for multiple cell types. A new method without the need of initial cell surface anchoring will greatly facilitate live cell surface labelling. Herein, we provide a general strategy for live cell functionalization that utilizes the native phosphate groups on every cell. We have designed a dual conjugation cargo molecule with a cationic side chain for non-covalent bonds with the negatively-charged cell surface and a phosphoric acid containing ligand for covalent bonding with the cell membrane phospholipid phosphate. Our dual conjugation strategy on live cell surfaces is non-toxic with enhanced stability to functionalize live cells. This provides a stable, reversible and reusable reagent with direct conjugation strategy to image live cell membranes.\n\nSignificanceThe ability to label live cell surfaces has many applications ranging from in vivo monitoring of cell populations to diagnostics and use of cells as drugs. Thus far, most reported strategies to label cell surfaces are not broadly applicable or easy to use for any cell type as it has relied on engineering cells with artificial moieties or conjugations that may affect cellular function. We provide a general solution to this long-standing problem by developing two-sided functionalization of the phosphate moieties that are ubiquitous on all cells. We show one application of our chemical strategy as a general-purpose live-cell membrane imaging reagent with long-time stability. Our strategy is broadly applicable to imaging, sensing, drug delivery, bioengineering, diagnostics and cell therapy.\n\nO_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

bioengineering↗