Mannose hyperbranched dendritic polymers interact with clustered organization of DC‐SIGN and inhibit gp120 binding

DC‐SIGN (dendritic cell‐specific ICAM‐3 grabbing non‐integrin) is a C‐type lectin receptor of dendritic cells and is involved in the initial steps of numerous infectious diseases. Surface plasmon resonance has been used to study the affinity of a glycodendritic polymer with 32 mannoses, to DC‐SIGN. This glycodendrimer binds to DC‐SIGN surfaces in the submicromolar range. This binding depends on a clustered organization of DC‐SIGN mimicking its natural organization as microdomain in the dendritic cells plasma membrane. Moreover, this compound inhibits DC‐SIGN binding to the HIV glycoprotein gp120 with an IC50 in the micromolar range and therefore can be considered as a potential antiviral drug.

[1]  Hugues Lortat-Jacob,et al.  Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. , 2002, Immunity.

[2]  Á. Corbí,et al.  C-Type Lectins DC-SIGN and L-SIGN Mediate Cellular Entry by Ebola Virus in cis and in trans , 2002, Journal of Virology.

[3]  Douglas S Kwon,et al.  DC-SIGN, a Dendritic Cell–Specific HIV-1-Binding Protein that Enhances trans-Infection of T Cells , 2000, Cell.

[4]  P. Schuck,et al.  Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and lamm equation modeling. , 2000, Biophysical journal.

[5]  J. Rojo,et al.  Glycodendritic structures: promising new antiviral drugs. , 2004, The Journal of antimicrobial chemotherapy.

[6]  J. Rojo,et al.  Mannosyl Glycodendritic Structure Inhibits DC-SIGN-Mediated Ebola Virus Infection in cis and in trans , 2003, Antimicrobial Agents and Chemotherapy.

[7]  Y. Kooyk,et al.  DC-SIGN: escape mechanism for pathogens , 2003, Nature Reviews Immunology.

[8]  P. Desprès,et al.  Dendritic‐cell‐specific ICAM3‐grabbing non‐integrin is essential for the productive infection of human dendritic cells by mosquito‐cell‐derived dengue viruses , 2003, EMBO reports.

[9]  Monique Nijhuis,et al.  Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells , 2004, The Journal of cell biology.

[10]  Daniel A. Mitchell,et al.  A Novel Mechanism of Carbohydrate Recognition by the C-type Lectins DC-SIGN and DC-SIGNR , 2001, The Journal of Biological Chemistry.

[11]  W. Weis,et al.  Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR , 2001, Science.

[12]  M. Monsigny,et al.  Carbohydrate-lectin interactions assessed by surface plasmon resonance. , 2003, Biochimie.

[13]  Kenneth A. Taylor,et al.  Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  O. Schwartz,et al.  DC-SIGN and L-SIGN Are High Affinity Binding Receptors for Hepatitis C Virus Glycoprotein E2* , 2003, Journal of Biological Chemistry.

[15]  P. Nieto,et al.  Glycodendritic structures based on Boltorn hyperbranched polymers and their interactions with Lens culinaris lectin. , 2003, Bioconjugate chemistry.

[16]  W. Weis,et al.  Extended Neck Regions Stabilize Tetramers of the Receptors DC-SIGN and DC-SIGNR* , 2005, Journal of Biological Chemistry.