Non-carbohydrate inhibitors of the lectin DC-SIGN.

Non-carbohydrate inhibitors of the lectin DC-SIGN. Research Abstract Details 

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Non-carbohydrate inhibitors of the lectin DC-SIGN. Abstract Text:

M Jack Borrok,Laura L Kiessling,M Jack Borrok,Laura L Kiessling,M Jack Borrok,Laura L Kiessling,

The C-type lectin dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is found on the surface of dendritic cells. It can mediate adhesion between dendritic cells and T lymphocytes and facilitate antigen capture and presentation. Many pathogens can exploit DC-SIGN binding for nefarious purposes. For example, DC-SIGN can facilitate the dissemination of viruses, like HIV-1. Alternatively, some microbes (e.g., Mycobacterium tuberculosis) use their ability to interact with DC-SIGN to evade immune detection. The diverse roles attributed to DC-SIGN provide impetus to identify ligands that can be used to explore its different functions. Such compounds also could serve as therapeutic leads. Most of the DC-SIGN ligands studied previously are mannose- or fucose-derived monosaccharides or oligosaccharides with inhibitory constants in the range of 0.1-10 mM. To identify monovalent ligands with more powerful DC-SIGN blocking properties, we devised a high-throughput fluorescence-based competition assay. This assay afforded potent non-carbohydrate, small molecule inhibitors (IC50 values of 1.6-10 microM). These compounds block not only DC-SIGN-carbohydrate interactions but also DC-SIGN-mediated cell adhesion. Thus, we anticipate that these non-carbohydrate inhibitors can be used to illuminate the role of DC-SIGN in pathogenesis and immune function.

Non-carbohydrate inhibitors of the lectin DC-SIGN. Publishing Authors By Initials

MJ Borrok,LL Kiessling,MJ Borrok,LL Kiessling,MJ Borrok,LL Kiessling,

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Non-carbohydrate inhibitors of the lectin DC-SIGN. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of the American Chemical Society

VOLUME: 129

Page Numbers: 12780-5

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 29

MONTH: 09

YEAR: 2007

Non-carbohydrate inhibitors of the lectin DC-SIGN. Information

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LANGUAGE: eng

NlmUniqueID: 7503056

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Grant and Affiliation Information for Non-carbohydrate inhibitors of the lectin DC-SIGN.

AFFILIATION: Department of Biochemistry and Chemistry, University of Wisconsin, Madison, WI 53706, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: T32 GM07215

ACRONYM: GM

MEDLINETA: J Am Chem Soc

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