A set of multivalent polyhydroxylated acetamidoazepanes based on ethylene glycol, glucoside, or cyclodextrin scaffolds was prepared. The compounds were assessed against plant, mammalian, and therapeutically relevant hexosaminidases. Multimerization was shown to improve the inhibitory potency with synergy, and to fine tune the selectivity profile between related hexosaminidases.
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http://dx.doi.org/10.1002/chem.201701756 | DOI Listing |
Mol Pharm
January 2025
Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota 55455, United States.
Selective delivery of therapeutic modalities to tumor cells via binding of tumor-selective cell-surface biomarkers has empowered substantial advances in cancer treatment. Yet, tumor cells generally lack a truly specific biomarker that is present in high density on tumor tissue while being completely absent from healthy tissue. Rather, low but nonzero expression in healthy tissues results in on-target, off-tumor activity with detrimental side effects that constrain the therapeutic window or prevent use altogether.
View Article and Find Full Text PDFBiomacromolecules
December 2024
Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
Targeted protein degradation (TPD) marks a shift in drug development from conventional inhibition to the complete removal of pathological proteins. Traditional TPD technologies target intracellular proteins of interest (POIs) for degradation but are ineffective against extracellular cell surface and soluble proteins, a significant portion of the human proteome. Recent advances involve the formation of ternary complexes between a POI and a cell surface lysosomal trafficking receptor, directing POIs to lysosomes for degradation.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Blood Transfusion, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
The spread of multidrug-resistant strains of poses a great challenge in gonorrhea treatment. At present, vaccination is the best strategy for gonorrhea control. However, given the extensive antigenic variability of , the effectiveness of monovalent vaccines is limited.
View Article and Find Full Text PDFAdv Sci (Weinh)
November 2024
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.
Dual Opdivo plus Yervoy immunotherapy, targeting the immune checkpoints PD1 and CTLA-4, is successful in clinical use. However, it is associated with a high incidence of adverse events, and its therapeutic efficacy needs improving. In this study, polymeric multivalent Fc-binding peptides (PLG-Fc-III-4C) are employed to fabricate a bispecific antibody (PD1/CTLA-4 BsAb) to potentiate dual immunotherapy targeting PD1 and CTLA-4.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
During repeated virus exposure, pre-existing antibodies can mask viral epitopes by competing with B cell receptors for antigen. Although this phenomenon has the potential to steer B cell responses away from conserved epitopes, the factors that influence epitope masking by competing antibodies remain unclear. Using engineered, influenza-reactive B cells, we investigate how antibodies influence the accessibility of epitopes on the viral surface.
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