Format

Send to

Choose Destination
Carbohydr Res. 2017 Dec 1;453-454:36-43. doi: 10.1016/j.carres.2017.10.017. Epub 2017 Oct 31.

Mannosylcalix[n]arenes as multivalent ligands for DC-SIGN.

Author information

1
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
2
Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 71 avenue des Martyrs, CS 10090, 38044 Grenoble Cedex 9, France.
3
Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 71 avenue des Martyrs, CS 10090, 38044 Grenoble Cedex 9, France. Electronic address: franck.fieschi@ibs.fr.
4
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy. Electronic address: francesco.sansone@unipr.it.

Abstract

DC-SIGN is a receptor protruded from the membrane of immature dendritic cells (DCs) that participates in the activation of the immune response through the recognition of pathogen-associated molecular patterns (PAMPs). On the other hand, HIV exploits the interaction between high-mannose structures of its envelope glycoprotein gp120 and DC-SIGN to be transported towards and infect T-cells. DC-SIGN is involved in the recognition process in the form of a tetramer and the multiple exposition of carbohydrate recognition sites (CRSs) is amplified by the formation on the DCs membrane of patches of tetramers. DC-SIGN is then considered an interesting target to fight the virus and multivalent systems exposing multiple copies of ligating units for its CRSs are becoming valuable tools to reach this goal. We herein prepared four mannosylated calix[n]arenes (1a-d) and tested them by Surface Plasmon Resonance (SPR) competition assays as inhibitors of the binding between DC-SIGN and a mannosylated BSA used as model of HIV gp120. IC50s in the μM range were found evidencing in particular for compound 1a that, although rather moderate, a multivalent effect is taking place in the inhibition activity of this cluster. A relative potency (rp/n) around 4, respect to the monovalent methyl α-mannoside and normalized for the number of monosaccharide on the scaffold, was observed. This result, compared with previously reported data relative to dendrimers with the same valency, indicates the calixarene as a promising scaffold to build efficient inhibitors for DC-SIGN and, in perspective, for HIV.

KEYWORDS:

DC-SIGN; Dendritic cells; Glycocalixarenes; Glycoside cluster effect; Multivalency

PMID:
29121497
DOI:
10.1016/j.carres.2017.10.017
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center