Targeting the carbohydrates on HIV-1: Interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN
Resource
Proceedings of the National Academy of Science, 105(10), 3690-3695
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
105
Journal Issue
10
Pages
3690
Date Issued
2008-03-25
Date
2008
Author(s)
Wang, Sheng-Kai
Astronomo, Rena D.
Hsu, Tsui-Ling
Hsieh, Shie-Liang
Burton, Dennis R.
Wong, Chi-Huey
Abstract
It is widely accepted that the heavily glycosylated glycoprotein gp120 on the surface of HIV-1 shields peptide epitopes from recognition by the immune system and may promote infection in vivo by interaction with dendritic cells and transport to tissue rich in CD4(+) T cells such as lymph nodes. A conserved cluster of oligomannose glycans on gp120 has been identified as the epitope recognized by the broadly HIV-1-neutralizing monoclonal antibody 2G12. Oligomannose glycans are also the ligands for DC-SIGN, a C-type lectin found on the surface of dendritic cells. Multivalency is fundamental for carbohydrate-protein interactions, and mimicking of the high glycan density on the virus surface has become essential for designing carbohydrate-based HIV vaccines and antiviral agents. We report an efficient synthesis of oligomannose dendrons, which display multivalent oligomannoses in high density, and characterize their interaction with 2G12 and DC-SIGN by a glycan microarray binding assay. The solution and the surface binding analysis of 2G12 to a prototype oligomannose dendron clearly demonstrated the efficacy of dendrimeric display. We further showed that these glycodendrons inhibit the binding of gp120 to 2G12 and recombinant dimeric DC-SIGN with IC(50) in the nanomolar range. A second-generation Man(9) dendron was identified as a potential immunogen for HIV vaccine development and as a potential antiviral agent.
SDGs
File(s)![Thumbnail Image]()
Loading...
Name
57.pdf
Size
23.18 KB
Format
Adobe PDF
Checksum
(MD5):2b5e5e1f708d5f87ef0aa37177d87521