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. 2010 Nov 14;15(2):347–360. doi: 10.1007/s11030-010-9285-y

Design, synthesis and activity evaluation of mannose-based DC-SIGN antagonists

Nataša Obermajer 1,2, Sara Sattin 3, Cinzia Colombo 3, Michela Bruno 3, Urban Švajger 4, Marko Anderluh 5,✉, Anna Bernardi 3,✉
PMCID: PMC7089406  PMID: 21076980

Abstract

In this article, we describe the design, synthesis and activity evaluation of glycomimetic DC-SIGN antagonists, that use a mannose residue to anchor to the protein carbohydrate recognition domain (CRD). The molecules were designed from the structure of the known pseudo-mannobioside antagonist 1, by including additional hydrophobic groups, which were expected to engage lipophilic areas of DC-SIGN CRD. The results demonstrate that the synthesized compounds potently inhibit DC-SIGN-mediated adhesion to mannan coated plates. Additionally, in silico docking studies were performed to rationalize the results and to suggest further optimization.

Electronic supplementary material

The online version of this article (doi:10.1007/s11030-010-9285-y) contains supplementary material, which is available to authorized users.

Keywords: Anti-infectives, Carbohydrates, DC-SIGN, Dendritic cell-based assay, Glycoconjugates, Glycomimetics

Electronic Supplementary Material

The Below is the Electronic Supplementary Material.

ESM 1 (DOC 917 kb) (916.5KB, doc)
ESM 2 (PDF 898 kb) (897.3KB, pdf)

Abbreviations

BSA

Bovine serum albumin

CFSE

Carboxyfluorescein succinimidyl ester

CRD

Carbohydrate- recognition domain

DC

Dendritic cell

DCC

Dicyclohexyl carbodiimide

DC-SIGN

Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin

DMA

N,N-Dimethylacetamide

DMAP

4-Dimethylaminopyridine

DMSO

Dimethyl sulfoxide

EDC

1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide

FBS

Fetal bovine serum

HATU

O-(7-Azabenzotriazole)- N,N,N′,N′ - tetramethyluronium hexafluorophosphate

LPS

Lipopolysaccharide

MCPBA

m-Chloroperoxybenzoic acid

PAMPs

Pathogen-associated molecular patterns

PBS

Phosphate buffered saline

PFP

Pentafluorophenyl

rhGM-CSF

Recombinant human granulocyte-macrophage colony-stimulating factor

rhIL-4

Recombinant human interleukin-4

RMSD

Root mean square deviation

SAR

Structure–activity relationship

SDS

Sodium dodecyl sulfate

SPR

Surface-plasmon resonance

THF

Tetrahydrofuran

TLC

Thin-layer chromatography

TLR

Toll-like receptor

ManLAM

Mannosylated lipoarabinomannan

TMSOTf

Trimethylsilyl triflate

Contributor Information

Marko Anderluh, Email: marko.anderluh@ffa.uni-lj.si.

Anna Bernardi, Email: anna.bernardi@unimi.it.

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Supplementary Materials

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ESM 2 (PDF 898 kb) (897.3KB, pdf)

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