| DC-SIGN Antagonists, a Potential New Class of Anti-Infectives. | |
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MedLine Citation:
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PMID: 22257062 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a type II C-type lectin that functions as an adhesion molecule located on dendritic cells (DCs). It enables some of the functions of DCs, including migration, pathogen recognition, internalisation and processing, and their binding to T cells. HIV-1 has been reported to enter DCs by being bound to DC-SIGN, escaping the normal lytic pathway in DCs' endosomes and avoiding the immune system defence system. A very similar mechanism of survival has been observed for some other pathogens. This makes DC-SIGN a receptor of interest in the design of distinctive anti-infectives that would inhibit DC-SIGN-pathogen interaction by blocking the very first step in pathogen infection. In this review we outline the development of DC-SIGN antagonists, focusing mainly on a glycomimetic approach. Based on the fact that DC-SIGN binds mannose- and fucose-based oligo- and polysaccharides, their structural mimics have been designed and proved to inhibit pathogen-DC-SIGN interaction. Furthermore, recent in vitro studies have demonstrated that DC-SIGN antagonists block effectively the transmission of pathogens like HIV-1 and Ebola to CD4+ T cells. Although DC-SIGN has not been validated in vivo as a druggable target yet, we await future DC-SIGN antagonists as a new and highly promising group of novel anti-infectives. |
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Authors:
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Marko Anderluh; Gregor Jug; Urban Svajger; Nataša Obermajer |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-17 |
Journal Detail:
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Title: Current medicinal chemistry Volume: - ISSN: 1875-533X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9440157 Medline TA: Curr Med Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Medicinal Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia. marko.anderluh@ffa.uni-lj.si. |
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