Biomimetic Carbohydrate‐Binding Agents (CBAs): Binding Affinities and Biological Activities

: With the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the whole world is suffering from atypical pneumonia, which resulted in more than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing new antivirals are a laborious task. Therefore, considering the high infection rate and mortality due to COVID-19, utilization of previous information, and repurposing of existing drugs against valid viral targets have emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs), which facilitates the virus’s entry into the host cells, exists in a homotrimeric form and is covered with N-linked glycans. S glycoprotein is known as the main target of antibodies having neutralizing potency and is also considered as an attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of S glycoprotein envelope of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have shown antiviral activities against CoV and other enveloped viruses. However, the potential use of CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity, hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we reviewed the current scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A) with Man9 by molecular docking for potential repurposing against CoVs in general, and SARSCoV- 2, in particular.

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Carbohydrate binding activities of Bradyrhizobium japonicum. II. Isolation and characterization of a galactose-specific lectin.

The Journal of Cell Biology ◽

10.1083/jcb.111.4.1639 ◽

1990 ◽

Vol 111 (4) ◽

pp. 1639-1643 ◽

Cited By ~ 25

Author(s):

S C Ho ◽

M Schindler ◽

J L Wang

Keyword(s):

Isoelectric Focusing ◽

Bradyrhizobium Japonicum ◽

Affinity Column ◽

Carbohydrate Binding ◽

Binding Affinities ◽

Isolation And Characterization ◽

Relative Binding ◽

Mannose Derivatives ◽

Derivatives Of

Extracts of Bradyrhizobium japonicum were fractionated on Sepharose columns covalently derivatized with lactose. Elution of the material that was specifically bound to the affinity column with lactose yielded a protein of Mr approximately 38,000. Isoelectric focusing of this sample yielded two spots with pI values of 6.4 and 6.8. This protein specifically bound to galactose-containing glycoconjugates, but did not bind either to glucose or mannose. Derivatives of galactose at the C-2 position showed much weaker binding; there was an 18-fold difference in the relative binding affinities of galactose versus N-acetyl-D-galactosamine. These results indicate that we have purified a newly identified carbohydrate-binding protein from Bradyrhizobium japonicum, that can exquisitely distinguish galactose from its derivatives at the C-2 position.

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Inhibition of infection and transmission of HIV-1 and lack of significant impact on the vaginal commensal lactobacilli by carbohydrate-binding agents

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkt152 ◽

2013 ◽

Vol 68 (9) ◽

pp. 2026-2037 ◽

Cited By ~ 8

Author(s):

M. I. Petrova ◽

L. Mathys ◽

S. Lebeer ◽

S. Noppen ◽

E. J. M. Van Damme ◽

...

Keyword(s):

Carbohydrate Binding ◽

Binding Agents ◽

Hiv 1

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New structural insights into anomeric carbohydrate recognition by frutalin: an α-d-galactose-binding lectin from breadfruit seeds

Biochemical Journal ◽

10.1042/bcj20180605 ◽

2019 ◽

Vol 476 (1) ◽

pp. 101-113 ◽

Cited By ~ 1

Author(s):

Antonio Eufrásio Vieira Neto ◽

Felipe Domingos de Sousa ◽

Humberto D'Muniz Pereira ◽

Frederico Bruno Mendes Batista Moreno ◽

Marcos Roberto Lourenzoni ◽

...

Keyword(s):

Amino Acids ◽

Biological Activities ◽

3D Structure ◽

Carbohydrate Binding ◽

X Ray Crystallography ◽

Multiple Binding Sites ◽

Multiple Binding ◽

New Perspective ◽

Dynamics Simulations ◽

Binding Lectin

Abstract Frutalin (FTL) is a multiple-binding lectin belonging to the jacalin-related lectin (JRL) family and derived from Artocarpus incisa (breadfruit) seeds. This lectin specifically recognizes and binds α-d-galactose. FTL has been successfully used in immunobiological research for the recognition of cancer-associated oligosaccharides. However, the molecular bases by which FTL promotes these specific activities remain poorly understood. Here, we report the whole 3D structure of FTL for the first time, as determined by X-ray crystallography. The obtained crystals diffracted to 1.81 Å (Apo-frutalin) and 1.65 Å (frutalin–d-Gal complex) of resolution. The lectin exhibits post-translational cleavage yielding an α- (133 amino acids) and β-chain (20 amino acids), presenting a homotetramer when in solution, with a typical JRL β-prism. The β-prism was composed of three 4-stranded β-sheets forming three antiparallel Greek key motifs. The carbohydrate-binding site (CBS) involved the N-terminus of the α-chain and was formed by four key residues: Gly25, Tyr146, Trp147 and Asp149. Together, these results were used in molecular dynamics simulations in aqueous solutions to shed light on the molecular basis of FTL-ligand binding. The simulations suggest that Thr-Ser-Ser-Asn (TSSN) peptide excision reduces the rigidity of the FTL CBS, increasing the number of interactions with ligands and resulting in multiple-binding sites and anomeric recognition of α-d-galactose sugar moieties. Our findings provide a new perspective to further elucidate the versatility of FTL in many biological activities.

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Single-Particle Identification of Encoded Nanospheres

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057109356806 ◽

2010 ◽

Vol 15 (2) ◽

pp. 218-223 ◽

Cited By ~ 1

Author(s):

Hendrik Hippchen ◽

Wiebke H. Pohl ◽

Peter J. Walla

Keyword(s):

Single Particle ◽

Correlation Spectroscopy ◽

Particle Identification ◽

Carbohydrate Binding ◽

Binding Affinities ◽

Focal Volume ◽

Receptor Ligand ◽

Ligand Interactions ◽

Particle Level ◽

20 Nm

Recently, it has been shown that 2-photon fluorescence correlation spectroscopy of single glycosylated 20-nm fluorescent spheres allows measurement of the relative carbohydrate binding affinities of unlabeled proteins and that these modified spheres can mimic the glycocalix of cell or virus surfaces. An especially useful extension would be the analysis of mixtures of nanospheres that each contain different fluorescent labels and are thus differentially “encoded.” If the surfaces of these encoded nanospheres are modified with various receptors, many different biomolecule-surface interactions and concurrent reactions can be measured quickly and simultaneously in a single-reaction vessel. An essential prerequisite for this general assay principle is the ability to identify with an accuracy of nearly 100% any encoded nanosphere present in a mixture on a single-particle level. Here the authors present a method that indeed allows certain identification of differently encoded nanospheres during single transits through the focal volume of a microscope objective (ø~200-500 nm) in aqueous solution. This opens the way for using the encoded nanospheres in 1-well measurements of a large variety of biomolecular receptor-ligand interactions, inhibition and concurrent reactions, and thus either for testing the behavior of ligands in a mimicked complex biomolecular environment or for a fast simultaneous measurement of a multitude of receptor-ligand interactions.

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