Warfare between Pathogens and Hosts: The Trickery of Sugars

Lee, Y. C.

doi:10.4052/tigg.22.95

Cited by 12 publications

(3 citation statements)

References 38 publications

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“…1c) (46). This principal Ca 2+ site fulfills the same role in the related dendritic cell C-type lectin DC-SIGN and other members of this family such as the endocytic asialoglycoprotein receptor of hepatocytes (47)(48)(49). Whether physiologic fluctuations in concentration of calcium ions may affect the level of binding activity of these two (and other) C-type lectins involved in immune or transport-efficacy regulation is an open question.…”

Section: Ca 2+ : Beyond Indirect Effects (Neutral Ligands)mentioning

confidence: 99%

The How and Why of Ca2+ Involvement in Lectin Activity

Gabius¹

2011

TIGG

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Cell surface glycans are biochemical signals for communication with the environment. They are translated into biological responses by first binding to lectins, this recognition process thereupon triggering ensuing post-binding signaling. The specificity of this interaction must necessarily be exquisite to preclude errors. Toward this end Ca 2+ is recruited to the realm of protein-carbohydrate interactions. Intriguingly, not one but different strategies how Ca 2+ assists in singling out the correct sugar ligands are operative. This review dissects the different ways Ca 2+ functions as an integral component of various lectinsʼ carbohydrate-binding domains. It spans the range from the role of Ca 2+ in structurally organizing the contact site without direct interaction to the ligand to interplays with charged and even neutral ligands. Finally, a case of an intricate network of up to four coordination bonds of Ca 2+ with a galactose moiety is presented.

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Section: Ca 2+ : Beyond Indirect Effects (Neutral Ligands)mentioning

confidence: 99%

The How and Why of Ca2+ Involvement in Lectin Activity

Gabius¹

2011

TIGG

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“…Carbohydrate−lectin interactions are involved in various biological recognitions and mediate many processes including cellular recognition, 1 adhesion, 2 signal transduction, 3 glycoprotein clearance, 4 immunomodulation, 5,6 inflammation, 7 and host−pathogen recognition. 8 To fully understand the biological implications of carbohydrate−lectin interactions in living organisms, it is imperative to investigate and profile their functions under physiological conditions. Moreover, a quantitative assessment of the variations in lectins expressed in different cell states and cell types is essential for elucidating their biological roles in disease development.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Evaluation of a Photoactive Probe with a Multivalent Carbohydrate for Capturing Carbohydrate–Lectin Interactions

Chang¹,

Lai²,

Chien

et al. 2013

Bioconjugate Chem.

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Lectins are ubiquitous carbohydrate-binding proteins of nonimmune origin that are characterized by their specific recognition of defined monosaccharide or oligosaccharide structures. However, the use of carbohydrates to study lectin has been restricted by the weak binding affinity and noncovalent character of the interaction between carbohydrates and lectin. In this report, we designed and synthesized a multifunctional photoaffinity reagent composed of a trialkyne chain, a masked latent amine group, and a photoreactive 3-trifluoromethyl-3-phenyl-diazirine group in high overall yield. Two well-defined chemistries, Huisgen-Sharpless click chemistry and amide bond coupling, were the key steps for installing the multivalent character and tag in our designed photoaffinity probe. The photolabeling results demonstrated that the designed probe selectively labeled the target lectin, RCA120 ( Ricinus communis Agglutinin), in an E. coli lysate and an asialoglycoprotein receptor (ASGP-R) on intact HepG2 cell membranes. Moreover, the probe also enabled the detection of weak protein-protein interactions between RCA120 and ovalbumin (OVA).

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“…Besides substitutions of the core ligand binding to lectins can further be enhanced by an increase in valency, especially when the topologies of lectin-site/ glycan displays match or ligands are presented in microdomains. [20][21][22][23] To probe into the relative effect of bi-to trivalency in the same experimental setting we included the three glycoclusters 56, 59, 60 into the test panel. The screening process was strategically designed in two levels of increasing biorelevance, starting with an inhibition assay in which the labeled lectin (in solution) in microtiter plate wells binds to a surface-presented ligand.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory potential of chemical substitutions at bioinspired sites of β-d-galactopyranose on neoglycoprotein/cell surface binding of two classes of medically relevant lectins

Giguère

André

Bonin

et al. 2011

Bioorganic & Medicinal Chemistry

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Galactose is the key contact site for plant AB-toxins and the human adhesion/growth-regulatory galectins. Natural anomeric extensions and 3'-substitutions enhance its reactivity, thus prompting us to test the potential of respective chemical substitutions of galactose in the quest to develop potent inhibitors. Biochemical screening of a respective glycoside library with 60 substances in a solid-phase assay was followed by examining the compounds' activity to protect cells from lectin binding. By testing 32 anomeric extensions, 18 compounds with additional 3'-substitution, three lactosides and two Lewis-type trisaccharides rather mild effects compared to the common haptenic inhibitor lactose were detected in both assays. When using trivalent glycoclusters marked enhancements with 6- to 8-fold increases were revealed for the toxin and three of four tested galectins. Since the most potent compound and also 3'-substituted thiogalactosides reduced cell growth of a human tumor line at millimolar concentrations, biocompatible substitutions and scaffolds will be required for further developments. The synthesis of suitable glycoclusters, presenting headgroups which exploit differences in ligand selection in interlectin comparison to reduce cross-reactivity, and the documented strategic combination of initial biochemical screening with cell assays are considered instrumental to advance inhibitor design.

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Warfare between Pathogens and Hosts: The Trickery of Sugars

Cited by 12 publications

References 38 publications

The How and Why of Ca2+ Involvement in Lectin Activity

The How and Why of Ca2+ Involvement in Lectin Activity

Synthesis and Evaluation of a Photoactive Probe with a Multivalent Carbohydrate for Capturing Carbohydrate–Lectin Interactions

Inhibitory potential of chemical substitutions at bioinspired sites of β-d-galactopyranose on neoglycoprotein/cell surface binding of two classes of medically relevant lectins

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