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drughunter.com

Bioisosteres Cheat Sheet

Bioisosteric replacement is a powerful strategy for optimizing physicochemical, pharmacological, and safety properties of drug candidates. In this article, we provide a bioisosteres cheat sheet comple...

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Chris De Savi on LinkedIn: #medicine #pharmaceuticals #healthcare | 90 comments

FDA Novel Drug Approvals 2024 #medicine That is a wrap for 2024! And another year of relentless drug discovery! There you have it, drug-hunting aficionados,… | 90 comments on LinkedIn

www.biorxiv.org

Lipid-directed covalent fluorescent labeling of plasma membranes for long-term imaging, barcoding and manipulation of cells

Fluorescent probes for cell plasma membrane (PM) are generally based on amphiphilic anchors that incorporate non-covalently into biomembranes. Therefore, they are not compatible with fixation and permeabilization, presence of serum, or cell co-culture because of their exchange with the medium. Here, we report a concept of lipid-directed covalent labeling of PM, which exploits transient binding to lipid membrane surface generating high local dye concentration, thus favoring covalent ligation to random proximal membrane proteins. This concept yielded a class of fluorescent probes for PM (MemGraft), where a cyanine dye (Cy3 and Cy5) bears at its two ends low-affinity membrane anchor and reactive group: an activated ester or a maleimide. We found that MemGraft probes with these reactive groups provide efficient PM labelling, in contrast to a series of control compounds, including commercial Cy3-based labels of amino and thiol groups, revealing the crucial role of the membrane anchor combined with high reactivity of activated ester and a maleimide groups. In contrast to conventional PM probes, based on non-covalent interactions, MemGraft labelling approach is compatible with cell fixation, permeabilization, trypsinization and presence of serum. The latter allows long-term cell tracking and video imaging of cell PM dynamics without signs of phototoxicity. The covalent strategy also enables staining and long-term tracking of co-cultured cells labelled in different colors without probes exchange. Moreover, combination of different ratios of MemGraft-Cy3 and MemGraft-Cy5 probes enabled long-term cell barcoding in at least 5 color codes, important for tracking and visualizing multiple cells populations. Ultimately, we found that MemGraft strategy enables efficient biotinylation of cell surface, opening the path to cell surface engineering and cell manipulation. ### Competing Interest Statement The authors have declared no competing interest.

media.tenor.com

a cartoon character from the emperor 's new groove is holding a fan and says boom baby

Alt: Emperor Cuzco from the animated movie "The Emperor's New Groove" bursts into a room shouting "BOOM BABY!", representing the american chemical society division of biochemistry and chemical biology's presence on BlueSky should be known, celebrated, and perhaps feared by the #chembio #chemsky #chemtwitter #chemicalbiology #realtimechem and other communities. The jovial reference to a children's movie likewise signifies the division's interest in making this online space fun and inclusive for scientists of all ages and career stages, and likely foretells of future memes to be posted by this account.