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Site-specific conjugation of bifunctional chelator BAT to mouse IgG1 Fab~1 fragment

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Acta Pharmacologica Sinica 2006年第2期27卷 237-241页

作者： Jun LI~1 Xue-hao WANG Xiao-ming WANG Zhao-lai CHEN Division of Hepatic Surgery.Department of Surgery,the First Affiliated Hospital of Nanjing Medical University and Jiangsu Province Hospital.Nanjing 210029.China Division of Hepatic Surgery Department of Surgery the First Affiliated Hospital of Nanjing Medical University and Jiangsu Province Hospital Nanjing 210029 China

Aim:To perform a site-specific conjugation of Fab’ fragments of a mouse mono-clonal antibody(MoAb)B43(of IgG1subtype)to a bifunctional chelator 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N′,N″,N′″-tetraacetic acid(BAT)via the thiol groups in the hinge distal to the antigen-binding site of the Fab~***:B43 was cleaved using a simple 2-step ***,stable F(ab~1)2was produced by pepsin ***~1 with tree thiol in thehinge region was then obtained by cysteine reduction of F(ab~1)***,a site-specific conjugation of Fab~1 to thiol-specific BAT was performed in a ***:The Fab~1 fragment had approximately 1.8 free thiol groups permolecule after cysteine *** conjugation efficiency and the chemicalyield were approximately 1.28 moles chelator/Fab′ and 74% of the initial concentra-tion of Fab′,*** F(ab′)2,Fab′ and Fab′-BAT all maintained reason-able antigen-binding properties.67Cu labeling of the conjugate under standardconditions did not impair the immunoreactivity of Fab′-***:This isa simple and efficient method for producing immunoreactive conjugates of Fab′-BAT,which can be used to make radiometal-labeled conjugates for further diag-nostic and therapeutic applications.

关键词： conjugation BAT chelator monoclonal antibody

Evaluation of a novel oral iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) for treatment of iron overload in mice

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Advances in Bioscience and Biotechnology 2013年第2期4卷 153-163页

作者： Somdet Srichairatanakool Kanjana Pangjit Chada Phisalaphong Suthat Fucharoen Department of Biochemistry Faculty of Medicine Chiang Mai University Chiang Mai Thailand Institute of Research and Development Government Pharmaceutical Organization Ministry of Public Health Bangkok Thailand Thalassemia Research Center Institute of Molecular Bioscience Mahidol University Salaya Campus Nakornpathom Thailand

Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are promising effective iron chelators for the treatment of iron overload in b-thalassemia patients;nonetheless, their side effects have also been reported. 3-Hydroxypyridinone derivatives are being developed as a safer new chelator and in combined chelation therapy. We evaluated the iron-chelating activity of 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) in iron-loaded C57BL6 mice. The feeding of a ferrocene-supplemented diet (Fe diet) to mice resulted in iron overload, detectable plasma nontransferrin-bound iron (NTBI) and labile plasma iron (LPI), and increases of red cell membrane iron, plasma malondialdehyde (MDA) and excessive tissue iron deposits. Like DFP, the CM1 lowered the levels of the membrane non-heme iron, the NTBI and LPI (p chelators did not change the morphology of the liver and heart. Numerous iron accumulations were observed in the liver and spleen tissues of the Fe dietfed mice, whereas the CM1 reduced such iron deposition. Thus, 1-(N-acetyl-6-aminohexyl)-3-hydro- xypyridin-4-one (CM1) can be considered a candidate bidentate oral iron chelator and is effective in the removal of toxic irons in blood compartment and tissues. The effectiveness and toxicity of the CM1 need to be investigated extensively in thalassemia mice and patients with iron overload.

关键词： Thalassemia Iron Overload Iron chelator Hydroxypyridinone Lipid Peroxidation Malondialdehyde

A Multifunctional Fluorescent chelator Targeting Metal-Aβ40 Aggregates

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A Multifunctional Fluorescent Chelator Targeting Metal-Aβ40...

Remediation of Heavy Metal (Cd, Cr, Cu, Co, and Ni) Ions from Kaolinite Clay Using Molecular Micelles chelators and D-Optimum Experimental Design

第一届全国生物物理化学会议暨生物物理化学发展战略研讨会

作者： Yong Zhang,Liyuan Chen,Wenxing Yin,Shibing Zhang,Changlin Liu~* Key Laboratory of Pesticide & Chemical Biology,Ministry of Education,School of Chemistry,Central China Normal University,Wuhan 430079,China

Increasing evidence indicates that the aggregation of amyloidβ-peptides(Aβ) and the production of reactive oxygen species by the copper-Aβaggregates are two important neurotoxic events in Alzheimer’s disease(AD).Because the Aβaggregation mediated by the metal ions including Cu and Zn is reversible,the generation and dissociation of Aβaggregates could be controlled by metal ***,metal chelation therapy using

关键词： AB metals aggregates fluorescent chelator

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Journal of Environmental Protection 2013年第8期4卷 789-795页

作者： Sayo O. Fakayode Ashley M. Taylor Maya McCoy Sri Lanka Owen Whitney E. Stapleton Carmen Grady David A. Pollard Department of Chemistry Winston-Salem State University Winston-Salem USA

This study investigated the potential utility of poly (sodium N-undecanoyl-L-leucyl-valinate) (poly-L-SULV), poly (sodium N-undecanoyl-L-leucyl-alanate) (poly-L-SULA), and poly (sodium N-undecanoyl-glycinate) (poly-SUG) molecular micelles (MMs) as chelators for heavy metal (Cd, Cr, Cu, Co, and Ni) ion remediation of kaolinite clay using D-optimum experimental design. D-optimum experimental design was employed to simultaneously investigate the influence of design variables such as the buffer pH, chelator concentration, and centrifuge speed to evaluate the optimum conditions and to reduce the time and cost of metal ion remediation. The partition coefficients of the metal ion concentrations between the kaolinite clay and chelator equilibrium were also evaluated. In addition, the influence of metal ion concentrations on the remediation capability of the chelators was evaluated by conducting remediation studies at four different (10 ppm, 40 ppm, 60 ppm, and 80 ppm) metal ion concentrations. In general, the results of the remediation efficiency and partition coefficients obtained in this study are highly metal ion dependent and also dependent upon the chelator used for the remediation. Specifically, the remediation efficiency of the molecular micelles was found to be comparable to or better than the corresponding remediation efficiency obtained when SDS or EDTA was used for the remediation. However, at optimum conditions, poly-SULV and poly-L-SULA molecular micelle chelators demonstrated superior remediation efficiencies for Cr, with remediation efficiency of 99.9 ± 8.7% and 99.1 ± 0.7%, respectively.

关键词： Heavy Metal Ion Remediation Molecular Micelles chelator D-Optimum Experimental Design Kaolinite Clay

The development of molecular and nano actinide decorporation agents

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Chinese Chemical Letters 2022年第7期33卷 3395-3404页

作者： Xiaomei Wang Cen Shi Jingwen Guan Yemeng Chen Yigong Xu Juan Diwu Shuao Wang State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences(RAD-X)and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou 215123China

Internal contamination of actinides has led to significant health hazards to the public and workers in the context of nuclear power plant accidents,uranium ore mining,and reprocessing of the used *** effective sequestering agent that is able to remove accidentally incorporated actinides in vivo with low toxicity is always in urgent *** molecular decorporation ligands have been the most widely researched agents for the past few decades,while preliminary studies of functionalized nanoparticles have shown their clear advantages in metal binding selectivity,toxicity,and oxidative stress ***,the state-of-the-art of those two types of decorporation agents is presented with special attention being paid on the correlation between the solution and solid-state chemistry of those agents with actinides and the corresponding decorporation efficacies.

关键词： Actinides chelator Binding selectivity Coordination mode Decorporation efficiency

Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded b-thalassemic mice

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Asian Pacific Journal of Tropical Biomedicine 2015年第12期5卷 1010-1017页

作者： Supranee Upanan Kanjana Pangjit Chairat Uthaipibull Suthat Fucharoen Andrew T.Mc Kie Somdet Srichairatanakool Department of Biochemistry Faculty of Medicine Chiang Mai University College of Medicine and Public Health Ubon Ratchathani University National Center for Genetic Engineering and Biotechnology National Science and Technology Development AgencyThailand Science Park Thalassemia Research Center Institute of Molecular Biosciences Mahidol University Salaya Campus Division of Diabetes and Nutritional Sciences School of Medicine King's College London

Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron overload in b-globin knockout thalassemic ***:The b-globin knockout thalassemic mice were fed with a ferrocenesupplemented diet for 2 months and oral administration of deionized water,DFP(50 mg/kg),CM1(50 mg/kg),GTE(50 mg epigallocatechin 3-gallate equivalent/kg),GTE along with DFP(50 mg/kg),and GTE along with CM1(50 mg/kg)every day for *** of hepatic Hamp1 m RNA,plasma non-transferrin bound iron,plasma alanine aminotransferase activity and tissue iron content were ***:All chelation treatments could reduce plasma non-transferrin bound iron ***,hepatic Hamp1 m RNA expression was significantly upregulated in the mice in a GTE+DFP combined treatment,correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron ***:The GTE+DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice,by chelating toxic iron in plasma and tissues,and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the *** is probably an advantage in giving GTE with DFP when treating patients with iron overload.

关键词： Thalassemia Iron overload Hepcidin Iron chelator G

Successful treatment of acute liver failure due to Wilson’s disease: Serendipity or fortuity?

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World Journal of Hepatology 2024年第8期16卷 1111-1119页

作者： Valeria Delle Cave Fabiola Di Dato Pier Luigi Calvo Maria Immacolata Spagnuolo Raffaele Iorio Department of Translational Medical Science Section of PediatricsUniversity of Naples Federico IINaples 80131Italy Pediatric Gastroenterology Unit Regina Margherita Children's HospitalAzienda Ospedaliera-Universitaria Cittàdella Salute e della ScienzaTurin 10126Italy

BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication for liver *** is no firm recommendation on specific and supportive medical treatment for this *** To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native *** A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to *** During the study period,16 children(9 males)received a diagnosis of WD and 2 of them presented with *** first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids,and survived without liver *** second,exclusively treated with supportive therapy,needed a hepatotransplant to overcome *** Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition,which is currently only treated with liver transplantation.

关键词： Fulminant liver failure Copper chelator Zinc Steroids Liver transplantation Autoimmune hepatitis Prognostic score 24 hour-urinary copper excretion Native liver

Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)in longterm iron loading β-thalassemic mice

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Asian Pacific Journal of Tropical Biomedicine 2014年第8期4卷 663-668页

作者： Kanokwan Kulprachakarn Nittaya Chansiw Kanjana Pangjit Chada Phisalaphong Suthat Fucharoen Robert C.Hider Sineenart Santitherakul Somdet Srichairatanakool Department of Biochemistry Faculty of MedicineChiang Mai UniversityChiang MaiThailand College of Medicine and Public Health Ubon Ratchathani UniversityUbon RatchathaniThailand Institute of Research and Development Government Pharmaceuticals OrganizationMinistry of Public HealthThailand Thalassemia Research Center Institute of Molecular BiosciencesMahidol University Salaya CampusNakornprathomThailand Institute of Pharmaceutical Science King's College LondonFranklin-Wilkins BuildingLondonUnited kingdom Medical Science Research Equipment Center Faculty of MedicineChiang Mai UniversityChiang MaiThailand

Objective:To evaluate the iron—chelating properties and free—radical scavenging activities of1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methyIpyridin—4-one(CM1) treatment in chronic iron-loaded β-thalassemic(BKO) ***:The BKO mice were fed with a ferrocene-rich diet and were orally administered with CM1|50 mg/(kg·day)| for 6 *** levels of non-transferrin hound iron,labile plasma ***(Ft) and malondialdehyde were ***:The BKO mice were fed with an iron diet for 8 months which resulted in iron ***,the mice showed a decrease in the non—transferrin bound iron,labile plasma iron and malondialdehyde levels,but not the Ft levels after continuous CM1 ***:CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overload β—thalassemic mice.

关键词： Iron-chelating Iron overload β-thalassemia Iron chelator Non-transferrin bound iron Lipid peroxidation

Wilson's disease:Revisiting an old friend

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World Journal of Hepatology 2021年第6期13卷 634-649页

作者： Ana Lucena-Valera Domingo Perez-Palacios Rocio Muñoz-Hernandez Manuel Romero-Gómez Javier Ampuero Department of Gastroenterology Hospital Universitario Virgen del RocioSevilla 41013Spain SeLiver Group Instituto de Biomedicina de Sevilla(IBiS)Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaEspaña Department of Unit of Digestive Diseases Hospital Universitario Virgen del RocioSevilla 41014Spain

Wilson's disease(WD)is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs,such as the central nervous *** is a hereditary autosomal recessive disease caused by a deficiency in the ATP7B *** protein facilitates the incorporation of copper into *** than 800 mutations associated with WD have been *** onset of the disease frequently includes manifestations related to the liver(as chronic liver disease or acute liver failure)and neurological symptoms,although it can sometimes be *** it being more frequent in young people,WD has been described in all life *** to its fatal prognosis,WD should be suspected in all patients with unexplained biochemical liver abnormalities or neurological or psychiatric *** diagnosis is established with a combination of clinical signs and tests,including the measurement of ceruloplasmin,urinary copper excretion,copper quantification in liver biopsy,or genetic *** pharmacological therapies include chelating drugs,such as D-penicillamine or trientine,and zinc salts,which are able to change the natural history of the disease,increasing the survival of these *** some cases of end-stage liver disease or acute liver failure,liver transplantation must be an option to increase *** this narrative review,we offer an overview of WD,focusing on the importance of clinical suspicion,the correct diagnosis,and treatment.

关键词： Wilson´s disease Copper ATP7B Ceruloplasmin chelator Liver disease