scholarly journals Correction: The barley lectin, horcolin, binds high-mannose glycans in a multivalent fashion, enabling high-affinity, specific inhibition of cellular HIV infection

2021 ◽  
Vol 297 (3) ◽  
pp. 101158
Author(s):  
Nisha Grandhi Jayaprakash ◽  
Amrita Singh ◽  
Rahul Vivek ◽  
Shivender Yadav ◽  
Sanmoy Pathak ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Specific Inhibition ◽  
High Affinity ◽  
High Mannose

scholarly journals The barley lectin, horcolin, binds high-mannose glycans in a multivalent fashion, enabling high-affinity, specific inhibition of cellular HIV infection

2020 ◽  
Vol 295 (34) ◽  
pp. 12111-12129
Author(s):  
Nisha Grandhi Jayaprakash ◽  
Amrita Singh ◽  
Rahul Vivek ◽  
Shivender Yadav ◽  
Sanmoy Pathak ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Binding Sites ◽  
Neutralizing Antibodies ◽  
Titration Calorimetry ◽  
Carbohydrate Binding ◽  
High Affinity ◽  
Mannose Binding ◽  
Surface Envelope ◽  
High Mannose ◽  
Anti Hiv

N-Linked glycans are critical to the infection cycle of HIV, and most neutralizing antibodies target the high-mannose glycans found on the surface envelope glycoprotein-120 (gp120). Carbohydrate-binding proteins, particularly mannose-binding lectins, have also been shown to bind these glycans. Despite their therapeutic potency, their ability to cause lymphocyte proliferation limits their application. In this study, we report one such lectin named horcolin (Hordeum vulgare lectin), seen to lack mitogenicity owing to the divergence in the residues at its carbohydrate-binding sites, which makes it a promising candidate for exploration as an anti-HIV agent. Extensive isothermal titration calorimetry experiments reveal that the lectin was sensitive to the length and branching of mannooligosaccharides and thereby the total valency. Modeling and simulation studies demonstrate two distinct modes of binding, a monovalent binding to shorter saccharides and a bivalent mode for higher glycans, involving simultaneous interactions of multiple glycan arms with the primary carbohydrate-binding sites. This multivalent mode of binding was further strengthened by interactions of core mannosyl residues with a secondary conserved site on the protein, leading to an exponential increase in affinity. Finally, we confirmed the interaction of horcolin with recombinant gp120 and gp140 with high affinity and inhibition of HIV infection at nanomolar concentrations without mitogenicity.

scholarly journals Proteomic Analysis of DC-SIGN on Dendritic Cells Detects Tetramers Required for Ligand Binding but No Association with CD4

2004 ◽  
Vol 279 (50) ◽  
pp. 51828-51835 ◽  
Author(s):  
Oliver K. Bernhard ◽  
Joey Lai ◽  
John Wilkinson ◽  
Margaret M. Sheil ◽  
Anthony L. Cunningham
Keyword(s):  
Dendritic Cells ◽  
Transmembrane Protein ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Lectin Receptors ◽  
High Affinity ◽  
Direct Binding ◽  
In Trans ◽  
High Mannose ◽  
Hiv Gp120

DC-SIGN (dendriticcellspecificintracellular adhesion molecule 3grabbingnon-integrin) or CD209 is a type II transmembrane protein and one of several C-type lectin receptors expressed by dendritic cell subsets, which bind to high mannose glycoproteins promoting their endocytosis and potential degradation. DC-SIGN also mediates attachment of HIV to dendritic cells and binding to this receptor can subsequently lead to endocytosis or enhancement of CD4/CCR5-dependent infection. The latter was proposed to be facilitated by an interaction between DC-SIGN and CD4. Endocytosis of HIV virions does not necessarily lead to their complete degradation. A proportion of the virions remain infective and can be later presented to T cells mediating their infectionin trans. Previously, the extracellular domain of recombinant DC-SIGN has been shown to assemble as tetramers and in the current study we use a short range covalent cross-linker and show that DC-SIGN exists as tetramers on the surface of immature monocyte-derived dendritic cells. There was no evidence of direct binding between DC-SIGN and CD4 either by cross-linking or by fluorescence resonance energy transfer measurements suggesting that there is no constitutive association of the majority of these proteins in the membrane. Importantly we also show that the tetrameric complexes, in contrast to DC-SIGN monomers, bind with high affinity to high mannose glycoproteins such as mannan or HIV gp120 suggesting that such an assembly is required for high affinity binding of glycoproteins to DC-SIGN, providing the first direct evidence that DC-SIGN tetramers are essential for high affinity interactions with pathogens like HIV.

scholarly journals Specific inhibition of FGF5-induced cell proliferation by RNA aptamers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryo Amano ◽  
Masato Namekata ◽  
Masataka Horiuchi ◽  
Minami Saso ◽  
Takuya Yanagisawa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Surface Plasmon Resonance ◽  
Growth Factor ◽  
Hair Growth ◽  
Rna Aptamers ◽  
Specific Inhibition ◽  
Fibroblast Growth ◽  
High Affinity ◽  
Systematic Evolution ◽  
Exponential Enrichment

AbstractFibroblast growth factor 5 (FGF5) is a crucial regulator of hair growth and an oncogenic factor in several human cancers. To generate FGF5 inhibitors, we performed Systematic Evolution of Ligands by EXponential enrichment and obtained novel RNA aptamers that have high affinity to human FGF5. These aptamers inhibited FGF5-induced cell proliferation, but did not inhibit FGF2-induced cell proliferation. Surface plasmon resonance demonstrated that one of the aptamers, F5f1, binds to FGF5 tightly (Kd = 0.7 ± 0.2 nM), but did not fully to FGF1, FGF2, FGF4, FGF6, or FGFR1. Based on sequence and secondary structure similarities of the aptamers, we generated the truncated aptamer, F5f1_56, which has higher affinity (Kd = 0.118 ± 0.003 nM) than the original F5f1. Since the aptamers have high affinity and specificity to FGF5 and inhibit FGF5-induced cell proliferation, they may be candidates for therapeutic use with FGF5-related diseases or hair disorders.

scholarly journals Monoclonal antibodies with subnanomolar affinity to tenofovir for monitoring adherence to antiretroviral therapies: from hapten synthesis to prototype development

2020 ◽  
Vol 8 (45) ◽  
pp. 10439-10449 ◽  
Author(s):  
Simone Cavalera ◽  
Consuelo Agulló ◽  
Josep V. Mercader ◽  
Fabio Di Nardo ◽  
Matteo Chiarello ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hiv Infection ◽  
Lateral Flow ◽  
Prototype Development ◽  
High Affinity ◽  
Antiretroviral Therapies ◽  
Hapten Synthesis

High-affinity antibodies were generated to develop enzymatic and lateral flow immunoassays for monitoring tenofovir, a drug commonly used for treating HIV infection and used as a biomarker of adherence to the therapy.

Generation of High Affinity Monoclonal Antibodies for the Prevention of HIV Infection

2009 ◽  
Vol 3 (2) ◽  
pp. 88-95 ◽  
Author(s):  
Nobuo Sakaguchi ◽  
Teppei Toda ◽  
Teruo Nakaya ◽  
Masataka Kitabatake ◽  
Kazuhiko Maeda ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hiv Infection ◽  
High Affinity ◽  
Prevention Of Hiv

scholarly journals A Yeast Glycoprotein Shows High-Affinity Binding to the Broadly Neutralizing Human Immunodeficiency Virus Antibody 2G12 and Inhibits gp120 Interactions with 2G12 and DC-SIGN

2009 ◽  
Vol 83 (10) ◽  
pp. 4861-4870 ◽  
Author(s):  
Robert J. Luallen ◽  
Hu Fu ◽  
Caroline Agrawal-Gamse ◽  
Innocent Mboudjeka ◽  
Wei Huang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Surface Plasmon Resonance Analysis ◽  
Peptide Epitopes ◽  
High Affinity ◽  
Immunodeficiency Virus ◽  
Gp120 Subunit ◽  
Neutralizing Monoclonal Antibody ◽  
High Mannose ◽  
Hiv 1 ◽  
Antibody 2G12

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein contains numerous N-linked carbohydrates that shield conserved peptide epitopes and promote trans infection by dendritic cells via binding to cell surface lectins. The potent and broadly neutralizing monoclonal antibody 2G12 binds a cluster of high-mannose-type oligosaccharides on the gp120 subunit of Env, revealing a conserved and highly exposed epitope on the glycan shield. To find an effective antigen for eliciting 2G12-like antibodies, we searched for endogenous yeast proteins that could bind to 2G12 in a panel of Saccharomyces cerevisiae glycosylation knockouts and discovered one protein that bound weakly in a Δpmr1 strain deficient in hyperglycosylation. 2G12 binding to this protein, identified as Pst1, was enhanced by adding the Δmnn1 deletion to the Δpmr1 background, ensuring the exposure of terminal α1,2-linked mannose residues on the D1 and D3 arms of high-mannose glycans. However, optimum 2G12 antigenicity was found when Pst1, a heavily N-glycosylated protein, was expressed with homogenous Man8GlcNAc2 structures in Δoch1 Δmnn1 Δmnn4 yeast. Surface plasmon resonance analysis of this form of Pst1 showed high affinity for 2G12, which translated into Pst1 efficiently inhibiting gp120 interactions with 2G12 and DC-SIGN and blocking 2G12-mediated neutralization of HIV-1 pseudoviruses. The high affinity of the yeast glycoprotein Pst1 for 2G12 highlights its potential as a novel antigen to induce 2G12-like antibodies.

Deficient expression of bactericidal/permeability-increasing protein in immunocompromised hosts: translational potential of replacement therapy

2011 ◽  
Vol 39 (4) ◽  
pp. 994-999 ◽  
Author(s):  
Christine D. Palmer ◽  
Eva C. Guinan ◽  
Ofer Levy
Keyword(s):  
Cystic Fibrosis ◽  
Hiv Infection ◽  
Bacterial Infection ◽  
Replacement Therapy ◽  
Lipid A ◽  
Immunocompromised Patient ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
High Affinity ◽  
Immunocompromised Hosts

BPI (bactericidal/permeability-increasing protein) is a 55 kDa anti-infective molecule expressed in neutrophil and eosinophil granules and on some epithelial cells. BPI's high affinity for the lipid A region of endotoxin targets its opsonizing, microbicidal and endotoxin-neutralizing activities towards Gram-negative bacteria. Several immunocompromised patient populations demonstrate BPI deficiency, including newborns, those with anti-neutrophil cytoplasmic antibodies (as in cystic fibrosis and HIV infection) and those exposed to radiochemotherapy. BPI may be replenished by administering agents that induce its expression or by administration of recombinant BPI congeners, potentially shielding BPI-deficient individuals against Gram-negative bacterial infection, endotoxemia and its toxic sequelae.

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