Development of C-type lectin-oriented surfaces for high avidity glycoconjugates: towards mimicking multivalent interactions on the cell surface

Porkolab, Vanessa; Pifferi, Carlo; Sutkevičiūtė, Ieva; Ordanini, Stefania; Taouai, Marwa; Thépaut, Michel; Vivès, Corinne; Benazza, Mohammed; Bernardi, Anna; Renaudet, Olivier; Fieschi, Franck

doi:10.1039/d0ob00781a

Cited by 35 publications

(63 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An IC 50 of 9.6±0.4 μM is estimated for the inhibition, which correlates with the apparent K D of DC-SIGN for the spike surfaces, which is here the reporting interaction ( Fig 6C ). In such competition test, it suggests that a higher avidity, towards DC-SIGN, can be awaited for PM26 [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

et al. 2021

Self Cite

View full text Add to dashboard Cite

The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.

show abstract

Section: Resultsmentioning

confidence: 99%

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the cell surface, Langerin oligomerizes into a trimer for high-affinity ligand engagement (Feinberg et al, 2010). Therefore, in the SPR assays, we made use of a trimeric Langerin ECD attached on the surfaces by the N-termini of their Neck domain, to mimic the natural presentation of the carbohydrate recognition domains at the cell membrane (Feinberg et al, 2011;Porkolab et al, 2020). In the direct interaction mode, where the Langerin ECD was bound to the sensor chip surface facing the ligands in the solvent, the apparent K d was calculated for the ligands.…”

Section: Resultsmentioning

confidence: 99%

“…The flow cells were functionalized with streptactin protein after EDC/NHS activation. Control flow cell 1 was functionalized with BSA, whereas another flow cell was functionalized with 100 µg/mL Langerin S-ECD via tag-specific capture and simultaneous amine coupling as previously described (Porkolab et al, 2020). An approximate density of about 2.609 RU was achieved on the chip surface.…”

Section: Surface Plasmon Resonance Analysismentioning

confidence: 99%

Targeting of the C-Type Lectin Receptor Langerin Using Bifunctional Mannosylated Antigens

Hogervorst

Achilli

et al. 2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Langerhans cells (LCs) are antigen-presenting cells that reside in the skin. They uniquely express high levels of the C-type lectin receptor Langerin (CD207), which is an attractive target for antigen delivery in immunotherapeutic vaccination strategies against cancer. We here assess a library of 20 synthetic, well-defined mannoside clusters, built up from one, two, and three of six monomannosides, dimannosides, or trimannosides, appended to an oligopeptide backbone, for binding with Langerin using surface plasmon resonance and flow cytometric quantification. It is found that Langerin binding affinity increases with increasing number of mannosides. Hexavalent presentation of the mannosides resulted in binding affinities ranging from 3 to 12 µM. Trivalent presentation of the dimannosides and trimannosides led to Langerin affinity in the same range. The model melanoma gp100 antigenic peptide was subsequently equipped with a hexavalent cluster of the dimannosides and trimannosides as targeting moieties. Surprisingly, although the bifunctional conjugates were taken up in LCs in a Langerin-dependent manner, limited antigen presentation to cytotoxic T cells was observed. These results indicate that targeting glycan moieties on immunotherapeutic vaccines should not only be validated for target binding, but also on the continued effects on biology, such as antigen presentation to both CD8 + and CD4 + T cells.

show abstract

“…The biological activity of glycodendrimers C1 and C2 towards DC-SIGN S-ECD and langerin S-ECD was assessed and compared with the corresponding linear constructs PM31 and PM26 by an established Surface Plasmon Resonance (SPR) direct interaction assay [25]. In this test, increasing concentrations of glycodendrimer solutions are flown over the surface of a sensor chip, functionalized with the immobilized targeted C-type lectins.…”

Section: Surface Plasmon Resonance Inhibition Studies With Dc-signmentioning

confidence: 99%

“…DC-SIGN and langerin extracellular domains harboured a StreptagII in their N-terminus (DC-SIGN S-ECD and langerin S-ECD) to allow their capture and functionalization onto the surface in an oriented manner. Flow cells were functionalized as previously described[25]. Briefly, after EDC/NHS activation, flow cells were functionalized with streptactin protein in a first step.…”

mentioning

confidence: 99%

Structure-Based Design of Glycodendrimer Antagonists for Improved DC-SIGN Targeting

Goti¹,

Colombo²,

Achilli³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

DC-SIGN multivalent antagonists have emerged as effective antiadhesive agents against various pathogen infections. Recently, our group have shown that high potency can be achieved upon bridging two of the four binding sites displayed by the protein. Here we present our endeavors to accomplish the tetracoordination of DC-SIGN through the synthesis of two cross-shaped glycodendrimers. The choice of a tailored rigid scaffold allowed multivalent presentation of glycomimetics in a spatially defined fashion, while providing good water solubility to the constructs. Evaluation of the biological activity by SPR assay revealed strong binding avidity towards DC-SIGN and increased selectivity over langerin.

show abstract

Development of C-type lectin-oriented surfaces for high avidity glycoconjugates: towards mimicking multivalent interactions on the cell surface

Abstract:
Here we described C-type lectin-oriented surfaces for SPR analysis. They allow the preservation of receptor topology, accessibility of binding sites, better evaluation of high avidity compounds and assessment of multivalent effect at cell surface.

Cited by 35 publications

References 32 publications

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Targeting of the C-Type Lectin Receptor Langerin Using Bifunctional Mannosylated Antigens

Structure-Based Design of Glycodendrimer Antagonists for Improved DC-SIGN Targeting

Contact Info

Product

Resources

About

Development of C-type lectin-oriented surfaces for high avidity glycoconjugates: towards mimicking multivalent interactions on the cell surface

Abstract: Here we described C-type lectin-oriented surfaces for SPR analysis. They allow the preservation of receptor topology, accessibility of binding sites, better evaluation of high avidity compounds and assessment of multivalent effect at cell surface.

Cited by 35 publications

References 32 publications

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Targeting of the C-Type Lectin Receptor Langerin Using Bifunctional Mannosylated Antigens

Structure-Based Design of Glycodendrimer Antagonists for Improved DC-SIGN Targeting

Contact Info

Product

Resources

About

Abstract:
Here we described C-type lectin-oriented surfaces for SPR analysis. They allow the preservation of receptor topology, accessibility of binding sites, better evaluation of high avidity compounds and assessment of multivalent effect at cell surface.