Synthesis and Detection of BODIPY-, Biotin-, and 19F- Labeled Single-Entity Dendritic Heparan Sulfate Mimetics
Congratulations to the authors of this week’s publication spotlight!
Dr. Sam Spijkers-Shaw, Dr. Rory Devlin, Dr. Nicholas J. Shields, Dr. Xiang Feng, Dr. Tessa Peck, Dr. Georgia Lenihan-Geels, Connor Davis, Prof. Sarah L. Young, Prof. Anne C. La Flamme, Dr. Olga V. Zubkova
Heparin and heparan sulfate (HS) are naturally occurring mammalian glycosaminoglycans, and their synthetic and semi-synthetic mimetics have attracted significant interest as potential therapeutics. However, understanding the mechanism of action by which HS, heparin, and HS mimetics have a biological effect is difficult due to their highly charged nature, broad protein interactomes, and variable structures. To address this, a library of novel single-entity dendritic mimetics conjugated to BODIPY, Fluorine-19 (19F), and biotin was synthesized for imaging and localization studies. The novel dendritic scaffold allowed for the conjugation of labeling moieties without reducing the number of sulfated capping groups, thereby better mimicking the multivalent nature of HS-protein interactions. The 19F labeled mimetics were assessed in phantom studies and were detected at concentrations as low as 5 mM. Flow cytometric studies using a fluorescently labeled mimetic showed that the compound associated with immune cells from tumors more readily than splenic counterparts and was directed to endosomal-lysosomal compartments within immune cells and cancer cells. Furthermore, the fluorescently labeled mimetic entered the central nervous system and was detectable in brain-infiltrating immune cells 24 hours after treatment. Here, we report the enabling methodology for rapidly preparing various labeled HS mimetics and molecular probes with diverse potential therapeutic applications.
The data was acquired on a cryogen-free MRS DRYMAG 7T at the University of Sydney. The article was published in Angewandte Chemie in 2024.
The publication is available at: https://doi.org/10.1002/anie.202316791
#MRI #drymag #cryogenfree #tumor