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  1. Article ; Online: Cell Culture-Based Assessment of Toxicity and Therapeutics of Phytochemical Antioxidants.

    Asuzu, Peace C / Trompeter, Nicholas S / Cooper, Carlton R / Besong, Samuel A / Aryee, Alberta N A

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 3

    Abstract: Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their ... ...

    Abstract Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.
    MeSH term(s) Animals ; Antioxidants/therapeutic use ; Antioxidants/toxicity ; Humans ; Oxidative Stress ; Phytochemicals/therapeutic use ; Phytochemicals/toxicity ; Plant Extracts/therapeutic use ; Plant Extracts/toxicity ; Toxicity Tests
    Chemical Substances Antioxidants ; Phytochemicals ; Plant Extracts
    Language English
    Publishing date 2022-02-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27031087
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cell Culture-Based Assessment of Toxicity and Therapeutics of Phytochemical Antioxidants

    Peace C. Asuzu / Nicholas S. Trompeter / Carlton R. Cooper / Samuel A. Besong / Alberta N. A. Aryee

    Molecules, Vol 27, Iss 1087, p

    2022  Volume 1087

    Abstract: Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their ... ...

    Abstract Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.
    Keywords medicinal plants ; antioxidant activity ; cell lines ; cytotoxicity ; apoptosis ; bioprinting ; Organic chemistry ; QD241-441
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency.

    Cai, Cindy X / Doria-Rose, Nicole A / Schneck, Nicole A / Ivleva, Vera B / Tippett, Brad / Shadrick, William R / O'Connell, Sarah / Cooper, Jonathan W / Schneiderman, Zachary / Zhang, Baoshan / Gowetski, Daniel B / Blackstock, Daniel / Demirji, Jacob / Lin, Bob C / Gorman, Jason / Liu, Tracy / Li, Yile / McDermott, Adrian B / Kwong, Peter D /
    Carlton, Kevin / Gall, Jason G / Lei, Q Paula

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 8433

    Abstract: CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody biological ... ...

    Abstract CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody biological activity. More importantly, here wedescribe for the first time the significance of the tyrosine-O-sulfation proteoforms. We developed a hydrophobic interaction chromatography (HIC) method to separate and quantify different sulfation proteoforms, which led to the direct functionality assessment of tyrosine-sulfated species. The fully sulfated (4-SO
    MeSH term(s) Animals ; Antibodies, Monoclonal/pharmacology ; Antibodies, Neutralizing ; Broadly Neutralizing Antibodies ; CHO Cells ; Cricetinae ; HIV Antibodies ; HIV-1 ; Tyrosine/chemistry
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Broadly Neutralizing Antibodies ; HIV Antibodies ; Tyrosine (42HK56048U)
    Language English
    Publishing date 2022-05-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-12423-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Community belongingness during COVID-19 predicts anxiety and depression treatment change in college students.

    McFayden, Tyler C / Rallis, Bethany A / Carlton, Corinne N / Ko, Hayoung / Breaux, Rosanna / Cooper, Lee / Ollendick, Thomas H / Sturgis, Ellie

    Psychotherapy research : journal of the Society for Psychotherapy Research

    2022  Volume 33, Issue 1, Page(s) 118–129

    Abstract: Objective: Community belongingness has been shown to be related to mental health outcomes in college students; however, little work has evaluated whether community belongingness impacts treatment change, especially during the COVID-19 pandemic, when ... ...

    Abstract Objective: Community belongingness has been shown to be related to mental health outcomes in college students; however, little work has evaluated whether community belongingness impacts treatment change, especially during the COVID-19 pandemic, when social isolation and mental health concerns are exacerbated. Accordingly, the current study evaluated community belongingness as a predictor of treatment change for anxiety and depression in a university counseling center.
    Method: Participants included 516 young adults with clinical levels of anxiety or depression who attended at least two individual therapy sessions at a university counseling center during fall 2020. Participants completed broad measures of psychosocial functioning at each session.
    Results: Paired-samples
    Conclusion: These results suggest improving community belongingness on college campuses may be a way to buffer mental health and improve treatment outcomes for students seeking psychological services. Specific clinical and educational recommendations for ways to improve community belongingness are discussed.
    MeSH term(s) Humans ; Male ; Female ; Young Adult ; Universities ; Students/psychology ; COVID-19/epidemiology ; Anxiety/psychology ; Anxiety/therapy ; Depression/psychology ; Depression/therapy ; Community Integration/psychology ; Social Isolation ; Mental Health/statistics & numerical data ; Counseling ; Treatment Outcome
    Language English
    Publishing date 2022-05-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 1080323-3
    ISSN 1468-4381 ; 1050-3307
    ISSN (online) 1468-4381
    ISSN 1050-3307
    DOI 10.1080/10503307.2022.2071654
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Experimental integrative muscular movement technique enhances cervical range of motion in patients with chronic neck pain: a pilot study.

    Rohe, Benjamin G / Carter, Ronald / Thompson, William R / Duncan, Randall L / Cooper, Carlton R

    Journal of alternative and complementary medicine (New York, N.Y.)

    2015  Volume 21, Issue 4, Page(s) 223–228

    Abstract: Introduction: Neck pain presents a tremendous physical and financial burden. This study compared the efficacy of the complementary and alternative medical treatments of integrative muscular movement technique (IMMT) and Swedish massage on neck pain in ... ...

    Abstract Introduction: Neck pain presents a tremendous physical and financial burden. This study compared the efficacy of the complementary and alternative medical treatments of integrative muscular movement technique (IMMT) and Swedish massage on neck pain in women of occupation age, the largest demographic group with neck pain.
    Methods: A total of 38 women were assigned to IMMT (n=28) or Swedish massage (n=10) in a blinded manner. Both groups received eight 30-minute treatments over 4 weeks. Cervical range of motion (ROM) in flexion, extension, sidebending, and rotation was measured before and after treatment. Each patient's pain was assessed by using an analogue pain scale of 0-10.
    Results: Compared with the Swedish massage group, patients receiving IMMT experienced a significant increase in ROM in cervical flexion (p<0.001), extension (p<0.001), sidebending (p<0.05), and rotation (p<0.001). Absolute change in pain for IMMT was -1.75 units compared with -0.3 units for Swedish massage (p<0.05).
    Conclusion: Patients receiving the IMMT demonstrated significantly improved cervical ROM in every movement measured compared with Swedish massage. Inclusion of the IMMT in a treatment regimen for chronic neck pain may lead to decreased pain and increased cervical ROM. These positive effects of the IMMT intervention may have a role in enhancing functional outcomes in patients with neck pain.
    MeSH term(s) Adult ; Cervical Vertebrae ; Chronic Pain/therapy ; Exercise Therapy ; Female ; Humans ; Massage ; Middle Aged ; Movement ; Neck/pathology ; Neck Pain/therapy ; Pain Measurement ; Pilot Projects ; Range of Motion, Articular ; Rotation ; Therapy, Soft Tissue ; Treatment Outcome ; Young Adult
    Language English
    Publishing date 2015-04
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1237383-7
    ISSN 1557-7708 ; 1075-5535
    ISSN (online) 1557-7708
    ISSN 1075-5535
    DOI 10.1089/acm.2014.0036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Diagnostic Accuracy of Clinical Pathways for Suspected Acute Myocardial Infarction in the Out-of-Hospital Environment.

    Alghamdi, Abdulrhman / Hann, Mark / Carlton, Edward / Cooper, Jamie G / Cook, Eloïse / Foulkes, Angela / Siriwardena, Aloysius N / Phillips, John / Thompson, Alexander / Bell, Steve / Kirby, Kim / Rosser, Andy / Body, Richard

    Annals of emergency medicine

    2023  Volume 82, Issue 4, Page(s) 439–448

    Abstract: Study objective: Chest pain is one of the most common reasons for emergency ambulance calls. Patients are routinely transported to the hospital to prevent acute myocardial infarction (AMI). We evaluated the diagnostic accuracy of clinical pathways in ... ...

    Abstract Study objective: Chest pain is one of the most common reasons for emergency ambulance calls. Patients are routinely transported to the hospital to prevent acute myocardial infarction (AMI). We evaluated the diagnostic accuracy of clinical pathways in the out-of-hospital environment. The Troponin-only Manchester Acute Coronary Syndromes decision aid and History, ECG, Age, Risk Factors, Troponin score require cardiac troponin (cTn) measurement, whereas the History and ECG-only Manchester Acute Coronary Syndromes decision aid and History, ECG, Age, Risk Factors score do not.
    Methods: We conducted a prospective diagnostic accuracy study at 4 ambulance services and 12 emergency departments between February 2019 and March 2020. We included patients who received an emergency ambulance response in whom paramedics suspected AMI. Paramedics recorded the data required to calculate each decision aid and took venous blood samples in the out-of-hospital environment. Samples were tested using a point-of-care cTn assay (Roche cobas h232) within 4 hours. The target condition was a diagnosis of type 1 AMI, adjudicated by 2 investigators.
    Results: Of 817 included participants, 104 (12.8%) had AMI. Setting the cutoff at the lowest risk group, Troponin-only Manchester Acute Coronary Syndromes had 98.3% sensitivity (95% confidence interval 91.1% to 100%) and 25.5% specificity (21.4% to 29.8%) for type 1 AMI. History, ECG, Age, Risk Factors, Troponin had 86.4% sensitivity (75.0% to 98.4%) and 42.2% specificity (37.5% to 47.0%); History and ECG-only Manchester Acute Coronary Syndromes had 100% sensitivity (96.4% to 100%) and 3.1% specificity (1.9% to 4.7%), whereas History, ECG, Age, Risk Factors had 95.1% sensitivity (88.9% to 98.4%) and 12.1% specificity (9.8% to 14.8%).
    Conclusion: With point-of-care cTn testing, decision aids can identify patients at a low risk of type 1 AMI in the out-of-hospital environment. When used alongside clinical judgment, and with appropriate training, such tools may usefully enhance out-of-hospital risk stratification.
    MeSH term(s) Humans ; Acute Coronary Syndrome/diagnosis ; Critical Pathways ; Prospective Studies ; Myocardial Infarction/diagnosis ; Troponin ; Hospitals
    Chemical Substances Troponin
    Language English
    Publishing date 2023-06-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603080-4
    ISSN 1097-6760 ; 0196-0644
    ISSN (online) 1097-6760
    ISSN 0196-0644
    DOI 10.1016/j.annemergmed.2023.04.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: External validation of the Manchester Acute Coronary Syndromes ECG risk model within a pre-hospital setting.

    Alotaibi, Ahmed / Alghamdi, Abdulrhman / Martin, Glen P / Carlton, Edward / Cooper, Jamie G / Cook, Eloïse / Siriwardena, Aloysius Niroshan / Phillips, John / Thompson, Alexander / Bell, Steve / Kirby, Kim Lucy / Rosser, Andy / Pennington, Elspeth / Body, Richard

    Emergency medicine journal : EMJ

    2023  Volume 40, Issue 6, Page(s) 431–436

    Abstract: Objectives: The Manchester Acute Coronary Syndromes ECG (MACS-ECG) prediction model calculates a score based on objective ECG measurements to give the probability of a non-ST elevation myocardial infarction (NSTEMI). The model showed good performance in ...

    Abstract Objectives: The Manchester Acute Coronary Syndromes ECG (MACS-ECG) prediction model calculates a score based on objective ECG measurements to give the probability of a non-ST elevation myocardial infarction (NSTEMI). The model showed good performance in the emergency department (ED), but its accuracy in the pre-hospital setting is unknown. We aimed to externally validate MACS-ECG in the pre-hospital environment.
    Methods: We undertook a secondary analysis from the Pre-hospital Evaluation of Sensitive Troponin (PRESTO) study, a multi-centre prospective study to validate decision aids in the pre-hospital setting (26 February 2019 to 23 March 2020). Patients with chest pain where the treating paramedic suspected acute coronary syndrome were included. Paramedics collected demographic and historical data and interpreted ECGs contemporaneously (as 'normal' or 'abnormal'). After completing recruitment, we analysed ECGs to calculate the MACS-ECG score, using both a pre-defined threshold and a novel threshold that optimises sensitivity to differentiate AMI from non-AMI. This was compared with subjective ECG interpretation by paramedics. The diagnosis of AMI was adjudicated by two investigators based on serial troponin testing in hospital.
    Results: Of 691 participants, 87 had type 1 AMI and 687 had complete data for paramedic ECG interpretation. The MACS-ECG model had a C-index of 0.68 (95% CI: 0.61 to 0.75). At the pre-determined cut-off, MACS-ECG had 2.3% (95% CI: 0.3% to 8.1%) sensitivity, 99.5% (95% CI: 98.6% to 99.9%) specificity, 40.0% (95% CI: 10.2% to 79.3%) positive predictive value (PPV) and 87.6% (87.3% to 88.0%) negative predictive value (NPV). At the optimal threshold for sensitivity, MACS-ECG had 50.6% sensitivity (39.6% to 61.5%), 83.1% specificity (79.9% to 86.0%), 30.1% PPV (24.7% to 36.2%) and 92.1% NPV (90.4% to 93.5%). In comparison, paramedics had a sensitivity of 71.3% (95% CI: 60.8% to 80.5%) with 53.8% (95% CI: 53.8% to 61.8%) specificity, 19.7% (17.2% to 22.45%) PPV and 93.3% (90.8% to 95.1%) NPV.
    Conclusion: Neither MACS-ECG nor paramedic ECG interpretation had a sufficiently high PPV or NPV to 'rule in' or 'rule out' NSTEMI alone.
    MeSH term(s) Humans ; Acute Coronary Syndrome/diagnosis ; Troponin T ; Prospective Studies ; Non-ST Elevated Myocardial Infarction ; Decision Support Techniques ; Troponin ; Emergency Service, Hospital ; Hospitals ; Electrocardiography ; Chest Pain/diagnosis ; Sensitivity and Specificity
    Chemical Substances Troponin T ; Troponin
    Language English
    Publishing date 2023-04-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2040124-3
    ISSN 1472-0213 ; 1472-0205
    ISSN (online) 1472-0213
    ISSN 1472-0205
    DOI 10.1136/emermed-2022-212872
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Soluble perlecan domain i enhances vascular endothelial growth factor-165 activity and receptor phosphorylation in human bone marrow endothelial cells

    Gomes Ronald R / Cooper Carlton R / Muthusamy Arivalagan

    BMC Biochemistry, Vol 11, Iss 1, p

    2010  Volume 43

    Abstract: Abstract Background Immobilized recombinant perlecan domain I (PlnDI) binds and modulates the activity of heparin-binding growth factors, in vitro . However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ... ...

    Abstract Abstract Background Immobilized recombinant perlecan domain I (PlnDI) binds and modulates the activity of heparin-binding growth factors, in vitro . However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ability of soluble forms to modulate vascular endothelial growth factor-165 (VEGF 165 ) enhanced capillary tube-like formation, and VEGF receptor-2 phosphorylation of human bone marrow endothelial cells, in vitro . Results In solution, PlnDI binds VEGF 165 in a heparan sulfate and pH dependent manner. Capillary tube-like formation is enhanced by exogenous PlnDI; however, PlnDI/VEGF 165 mixtures combine to enhance formation beyond that stimulated by either PlnDI or VEGF 165 alone. PlnDI also stimulates VEGF receptor-2 phosphorylation, and mixtures of PlnDI/VEGF 165 reduce the time required for peak VEGF receptor-2 phosphorylation (Tyr-951), and increase Akt phosphorylation. PlnDI binds both immobilized neuropilin-1 and VEGF receptor-2, but has a greater affinity for neuropilin-1. PlnDI binding to neuropilin-1, but not to VEGF receptor-2 is dependent upon the heparan sulfate chains adorning PlnDI. Interestingly, the presence of VEGF 165 but not VEGF 121 significantly enhances PlnDI binding to Neuropilin-1 and VEGF receptor-2. Conclusions Our observations suggest soluble forms of PlnDI are biologically active. Moreover, PlnDI heparan sulfate chains alone or together with VEGF 165 can enhance VEGFR-2 signaling and angiogenic events, in vitro . We propose PlnDI liberated during basement membrane or extracellular matrix turnover may have similar activities, in vivo .
    Keywords Biochemistry ; QD415-436 ; Organic chemistry ; QD241-441 ; Chemistry ; QD1-999 ; Science ; Q ; DOAJ:Biochemistry ; DOAJ:Life Sciences ; DOAJ:Biology and Life Sciences ; Animal biochemistry ; QP501-801
    Subject code 616
    Language English
    Publishing date 2010-11-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Soluble perlecan domain I enhances vascular endothelial growth factor-165 activity and receptor phosphorylation in human bone marrow endothelial cells.

    Muthusamy, Arivalagan / Cooper, Carlton R / Gomes, Ronald R

    BMC biochemistry

    2010  Volume 11, Page(s) 43

    Abstract: Background: Immobilized recombinant perlecan domain I (PlnDI) binds and modulates the activity of heparin-binding growth factors, in vitro. However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ability of ... ...

    Abstract Background: Immobilized recombinant perlecan domain I (PlnDI) binds and modulates the activity of heparin-binding growth factors, in vitro. However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ability of soluble forms to modulate vascular endothelial growth factor-165 (VEGF165) enhanced capillary tube-like formation, and VEGF receptor-2 phosphorylation of human bone marrow endothelial cells, in vitro.
    Results: In solution, PlnDI binds VEGF165 in a heparan sulfate and pH dependent manner. Capillary tube-like formation is enhanced by exogenous PlnDI; however, PlnDI/VEGF165 mixtures combine to enhance formation beyond that stimulated by either PlnDI or VEGF165 alone. PlnDI also stimulates VEGF receptor-2 phosphorylation, and mixtures of PlnDI/VEGF165 reduce the time required for peak VEGF receptor-2 phosphorylation (Tyr-951), and increase Akt phosphorylation. PlnDI binds both immobilized neuropilin-1 and VEGF receptor-2, but has a greater affinity for neuropilin-1. PlnDI binding to neuropilin-1, but not to VEGF receptor-2 is dependent upon the heparan sulfate chains adorning PlnDI. Interestingly, the presence of VEGF165 but not VEGF121 significantly enhances PlnDI binding to Neuropilin-1 and VEGF receptor-2.
    Conclusions: Our observations suggest soluble forms of PlnDI are biologically active. Moreover, PlnDI heparan sulfate chains alone or together with VEGF165 can enhance VEGFR-2 signaling and angiogenic events, in vitro. We propose PlnDI liberated during basement membrane or extracellular matrix turnover may have similar activities, in vivo.
    MeSH term(s) Bone Marrow Cells/cytology ; Endothelial Cells/cytology ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Heparan Sulfate Proteoglycans/chemistry ; Heparan Sulfate Proteoglycans/isolation & purification ; Heparan Sulfate Proteoglycans/metabolism ; Heparan Sulfate Proteoglycans/pharmacology ; Heparitin Sulfate/metabolism ; Humans ; Neovascularization, Physiologic/drug effects ; Phosphorylation/drug effects ; Protein Structure, Tertiary ; Signal Transduction/drug effects ; Solubility ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism
    Chemical Substances Heparan Sulfate Proteoglycans ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; perlecan (143972-95-6) ; Heparitin Sulfate (9050-30-0) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
    Language English
    Publishing date 2010-11-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041216-2
    ISSN 1471-2091 ; 1471-2091
    ISSN (online) 1471-2091
    ISSN 1471-2091
    DOI 10.1186/1471-2091-11-43
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency

    Cindy X. Cai / Nicole A. Doria-Rose / Nicole A. Schneck / Vera B. Ivleva / Brad Tippett / William R. Shadrick / Sarah O’Connell / Jonathan W. Cooper / Zachary Schneiderman / Baoshan Zhang / Daniel B. Gowetski / Daniel Blackstock / Jacob Demirji / Bob C. Lin / Jason Gorman / Tracy Liu / Yile Li / Adrian B. McDermott / Peter D. Kwong /
    Kevin Carlton / Jason G. Gall / Q. Paula Lei

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 11

    Abstract: Abstract CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody ... ...

    Abstract Abstract CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody biological activity. More importantly, here wedescribe for the first time the significance of the tyrosine-O-sulfation proteoforms. We developed a hydrophobic interaction chromatography (HIC) method to separate and quantify different sulfation proteoforms, which led to the direct functionality assessment of tyrosine-sulfated species. The fully sulfated (4-SO3) proteoform demonstrated the highest in vitro relative antigen binding potency and neutralization efficiency against a panel of HIV-1 viruses. Interestingly, highly variable levels of 4-SO3 were produced by different clonal CHO cell lines, which helped the bNAb process development towards production of a highly potent CAP256V2LS clinical product with high 4-SO3 proteoform. This study presents powerful insight for any biotherapeutic protein development where sulfation may play an important role in product efficacy.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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