Dendritic cell-specific, intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a C-type lectin expressed specifically on dendritic cells. It is a primary site for recognition and binding of various pathogens and thus a promising therapeutic target for inhibition of pathogen entry and subsequent prevention of immune defense cell infection. We report the design and synthesis of d-mannose-based DC-SIGN antagonists bearing diaryl substituted 1,3-diaminopropanol or glycerol moieties incorporated to target the hydrophobic groove of the receptor. The designed glycomimetics were evaluated by in vitro assay of the isolated DC-SIGN extracellular domain for their ability to compete with HIV-1 gp120 for binding to the DC-SIGN carbohydrate recognition domain. Compounds 14d and 14e, that display IC50 values of 40 μM and 50 μM, are among the most potent monovalent DC-SIGN antagonists reported. The antagonistic effect of all the synthesized compounds was further evaluated by a one-point in vitro assay that measures DC adhesion. Compounds 14d, 14e, 18d and 18e were shown to act as functional antagonists of DC-SIGN-mediated DC adhesion. The binding mode of 14d was also studied by molecular docking and molecular dynamics simulation, which revealed flexibility of 14d in the binding site and provides a basis for further optimization.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2014.01.047 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unprecedented selectivity for homologous lectin targets: differential targeting of the viral receptors L-SIGN and DC-SIGN.
Chem Sci
August 2024
Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale Grenoble France
DC-SIGN (CD209) and L-SIGN (CD209L) are two C-type lectin receptors (CLRs) that facilitate SARS-CoV-2 infections as viral co-receptors. SARS-CoV-2 manipulates both DC-SIGN and L-SIGN for enhanced infection, leading to interest in developing receptor antagonists. Despite their structural similarity (82% sequence identity), they function differently.
View Article and Find Full Text PDFC-based Multivalent Glycoporphyrins Inhibit SARS-CoV-2 Specific Interaction with the DC-SIGN Transmembrane Receptor.
Small
May 2024
Departamento de Química Orgánica, Facultad de Química, Universidad Complutense, Madrid, E-28040, Spain.
Since WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry.
View Article and Find Full Text PDFInhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells.
Cells
November 2021
The Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia.
The O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte derived dendritic cells (moDCs).
View Article and Find Full Text PDFPlant lectins as prospective antiviral biomolecules in the search for COVID-19 eradication strategies.
Biomed Pharmacother
February 2022
Department of Biotechnology & Genetic Engineering, University of Development Alternative, Dhaka, Bangladesh. Electronic address:
Lectins or clusters of carbohydrate-binding proteins of non-immune origin are distributed chiefly in the Plantae. Lectins have potent anti-infectivity properties for several RNA viruses including SARS-CoV-2. The primary purpose of this review is to review the ability of lectins mediated potential biotherapeutic and bioprophylactic strategy against coronavirus causing COVID-19.
View Article and Find Full Text PDFGlycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study.
Biomolecules
October 2021
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China.
Glycosylation is an important post-translational modification that affects a wide variety of physiological functions. DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a protein expressed in antigen-presenting cells that recognizes a variety of glycan epitopes. Until now, the binding of DC-SIGN to SARS-CoV-2 Spike glycoprotein has been reported in various articles and is regarded to be a factor in systemic infection and cytokine storm.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!