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Selective fluorination of Fc glycans enhances antibody-mediated effector functions – Research

Dr AF Saeed
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Selective fluorination of Fc glycans enhances antibody-mediated effector functions – Research


Antibody effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and various complement-dependent activities are critically influenced by the structure and composition of Fc N-glycans. Terminal galactosylation is generally associated with enhanced FcγRIIIA binding and C1q recruitment, thereby improving antibody activities. Recent structural studies suggest that terminal galactose can restrict glycan flexibility and stabilize Fc conformation by interacting with CH2 domain residues, thereby reducing the entropic penalty for FcγRIIIA binding. Motivated by this structural insight, we hypothesized that fine-tuning galactose-mediated Fc glycan-Fc domain interactions via site-selective fluorination could further modulate Fc-receptor and Fc-complement interactions. To test this, we developed a chemoenzymatic glycoengineering approach to generate homogeneous antibodies bearing precisely fluorinated Fc N-glycans. Key to this strategy was the chemical synthesis of position-specific fluorinated full-length Fc glycans, which were subsequently installed onto the antibody via enzymatic Fc glycan remodeling catalyzed by a glycosynthase mutant. Using this platform, we constructed a panel of homogeneous fluorinated antibodies and evaluated their functional consequences. ELISA-based binding assays revealed that fluorination at the C2 or C6 position of terminal galactose significantly increased FcγRIIIA affinity. Corresponding enhancements in ADCC were confirmed using a cell-based reporter bioassay. Furthermore, fluorination at these positions also promoted C1q binding and elevated the antibody-dependent cellular phagocytosis potency in whole blood assays. These results collectively demonstrate that selective Fc glycan fluorination represents a unique strategy to enhance antibody effector functions, providing a paradigm for precision glycoengineering in antibody therapeutics.


Keywords:

ADCC; CDCP; Fc glycosylation; antibody glyco-engineering; fluorinated glycans.



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NIT Tiruchirappalli Recruitment 2026 Notification Released for Faculty Posts at nitt.edu, Check Apply Online Date, Eligibility and More – Jagran Josh – Open Positions

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NIT Tiruchirappalli Recruitment 2026 Notification Released for Faculty Posts at nitt.edu, Check Apply Online Date, Eligibility and More – Jagran Josh – Open Positions



NIT Tiruchirappalli Recruitment 2026 Notification Released for Faculty Posts at nitt.edu, Check Apply Online Date, Eligibility and More  Jagran Josh



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Selective fluorination of Fc glycans enhances antibody-mediated effector functions – Research

Dr AF Saeed
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0
Selective fluorination of Fc glycans enhances antibody-mediated effector functions – Research


Antibody effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and various complement-dependent activities are critically influenced by the structure and composition of Fc N-glycans. Terminal galactosylation is generally associated with enhanced FcγRIIIA binding and C1q recruitment, thereby improving antibody activities. Recent structural studies suggest that terminal galactose can restrict glycan flexibility and stabilize Fc conformation by interacting with CH2 domain residues, thereby reducing the entropic penalty for FcγRIIIA binding. Motivated by this structural insight, we hypothesized that fine-tuning galactose-mediated Fc glycan-Fc domain interactions via site-selective fluorination could further modulate Fc-receptor and Fc-complement interactions. To test this, we developed a chemoenzymatic glycoengineering approach to generate homogeneous antibodies bearing precisely fluorinated Fc N-glycans. Key to this strategy was the chemical synthesis of position-specific fluorinated full-length Fc glycans, which were subsequently installed onto the antibody via enzymatic Fc glycan remodeling catalyzed by a glycosynthase mutant. Using this platform, we constructed a panel of homogeneous fluorinated antibodies and evaluated their functional consequences. ELISA-based binding assays revealed that fluorination at the C2 or C6 position of terminal galactose significantly increased FcγRIIIA affinity. Corresponding enhancements in ADCC were confirmed using a cell-based reporter bioassay. Furthermore, fluorination at these positions also promoted C1q binding and elevated the antibody-dependent cellular phagocytosis potency in whole blood assays. These results collectively demonstrate that selective Fc glycan fluorination represents a unique strategy to enhance antibody effector functions, providing a paradigm for precision glycoengineering in antibody therapeutics.


Keywords:

ADCC; CDCP; Fc glycosylation; antibody glyco-engineering; fluorinated glycans.



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Cofilin-1 is a redox-sensitive guard of the NLRP3 inflammasome – Immunology Research

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Cofilin-1 is a redox-sensitive guard of the NLRP3 inflammasome – Immunology Research


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    Scientists Just Built Atom-Sized Gates That Act Like Living Cells – Science News

    Dr AF Saeed
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    Scientists Just Built Atom-Sized Gates That Act Like Living Cells – Science News



    In-Pore Precipitation Reaction in a Solid-State NanoporeScientists have built atom-sized pores that act like living ion channels, opening the door to next-generation nanotech. Ion channels are extremely narrow pathways that are essential for many processes in living systems. To understand how ions move through these confined spaces, scientists need to build artificial pores at incredibly small scales. The tightest parts of […]



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    Subsequent SARS-CoV-2 Infection in Healthcare Workers: A Retrospective Cohort Study in Iran – Research

    Dr AF Saeed
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    Selective fluorination of Fc glycans enhances antibody-mediated effector functions – Research



    Background:

    The evolution of SARS-CoV-2 has increased global COVID-19 case prevalence. Healthcare workers (HCWs) are particularly susceptible to reinfection due to their exposure to infected patients. This study aimed to explore the risk factors for subsequent SARS-CoV-2 infection among HCWs.


    Methods:

    This retrospective study was conducted in a teaching hospital affiliated with the Iran University of Medical Sciences between March 2021 and October 2021. HCWs completed an online survey to gather information about their COVID-19 infection history. Subsequent SARS-CoV-2 infection was defined as two or more infections, regardless of the time frame interval. Individuals who experienced a second infection within 90 days of the initial infection were considered to have a recurrence, and others were considered to have a reinfection. The generalized estimation equation was utilized to develop a multivariable prediction model.


    Results:

    A total of 601 HCWs (60.2% female), mostly aged 18-29 years (47.4%), participated in this study. We observed 90 episodes of subsequent SARS-CoV-2 infection among HCWs, including 72 individuals (11.98%). Among them, 9 participants (1.5%) experienced recurrence, while 43 participants (7.1%) reported reinfection. In the multivariable analysis, vaccination significantly reduced the risk of subsequent SARS-CoV-2 infection, whereas nurses and those working in COVID-19 wards faced twice the risk.


    Conclusion:

    The frequency of subsequent SARS-CoV-2 infection is significant among HCWs. Vaccination status, occupation type, and workplace are key factors influencing the risk of future infections.


    Keywords:

    COVID‐19; SARS‐CoV‐2; healthcare workers; occupational risk; pandemic; public health; reinfection; risk factors; vaccination.



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    Resurrected 3.2-Billion-Year-Old Enzyme Could Unlock the Origins of Life – Science News

    Dr AF Saeed
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    Resurrected 3.2-Billion-Year-Old Enzyme Could Unlock the Origins of Life – Science News



    Abstract Origin of Life CellsBy reconstructing ancient nitrogen-processing enzymes, scientists are uncovering new clues about how early life survived on a very different Earth. Nitrogen is essential for life on Earth, yet most organisms cannot use it directly from the atmosphere. Scientists now believe this element may also provide important clues about how life first developed on our planet […]



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    Hyperoside Attenuates Lupus Nephritis-Associated Mesangial Cell Apoptosis via the P53/XAF1 Pathway: Integrative Bioinformatics and In Vitro Validation – Research

    Dr AF Saeed
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    Selective fluorination of Fc glycans enhances antibody-mediated effector functions – Research



    Objective:

    This study aimed to explore potential molecular targets and pathways of Hyp in LN using integrative bioinformatics and network pharmacology, and to provide in vitro validation of key mechanistic hypotheses in an IFN-α-induced mesangial-cell injury model.


    Methods:

    Differential expression analysis was performed on multiple datasets to identify LN-related target genes. Integrative approaches including machine learning algorithms, network pharmacology, and molecular docking were employed to explore the binding interactions between Hyp and target proteins. In vitro experiments were conducted to validate the mechanism by which Hyp intervenes in glomerular mesangial cell apoptosis.


    Results:

    A total of 18 genes were identified as potential targets involved in Hyp-induced modulation of LN progression. Machine learning SHAP analysis identified 5 core genes (STAT1, RSAD2, OAS3, GBP1, XAF1) as key regulators. Molecular docking simulations revealed specific binding between Hyp and each target protein, with particularly strong binding affinity between Hyp and XAF1. Cellular experimental results demonstrated that Hyp could inhibit the P53/XAF1 signaling pathway, downregulate the expression of apoptosis-related proteins, and thereby alleviate glomerular mesangial cell apoptosis.


    Conclusion:

    Hyp attenuated IFN-α-induced glomerular mesangial cell apoptosis by suppressing the P53/XAF1 signaling pathway, suggesting a potential therapeutic mechanism in LN. These integrative bioinformatics and in vitro findings provide a rationale for future in vivo validation and clinical translation.


    Keywords:

    P53/XAF1; apoptosis; glomerular mesangial cells; hyperoside; lupus nephritis.



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    Scientists Uncover Aging Link That Could Change How Cancer Is Treated – Science News

    Dr AF Saeed
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    Scientists Uncover Aging Link That Could Change How Cancer Is Treated – Science News



    Lung Cancer Tumor DiseaseA new study reveals how aging changes the biological behavior of lung cancer. Scientists at the University of Gothenburg have identified a protein that may increase the risk of lung cancer spreading and returning after treatment. Their findings suggest a possible path toward more targeted therapies, especially for older patients. Lung cancer is most common […]



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    Thermodynamic prediction of RNA cellular activity from sequence via conformational ensembles – Research

    Dr AF Saeed
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    Thermodynamic prediction of RNA cellular activity from sequence via conformational ensembles – Research



    The RNA sequence of HIV-1 TAR was systematically altered to change its propensity to adopt a functional secondary structure in the ensemble, measured using 1H CEST NMR. These minor sequence changes shifted the active-state propensity by ∼500-fold, quantitatively predicting changes in protein binding and cellular transactivation. These propensities could be inferred from secondary-structure prediction algorithms and incorporated into a thermodynamic framework to quantitatively predict how sequence changes alter protein-binding affinity and RNA cellular activity.



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