Дисертації з теми "Human carbonic anhydrase"
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Lusby, Paul J. "Synthetic models of human carbonic anhydrase II." Thesis, University of York, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326542.
Повний текст джерелаHammond, Jessica Ann. "Modelling the secondary coordination sphere of human carbonic anhydrase II." Thesis, University of York, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516636.
Повний текст джерелаMondal, Utpal Kumar. "CARBONIC ANHYDRASE MODULATORS FOR DETECTION AND TREATMENT OF HUMAN DISEASES." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/543241.
Повний текст джерелаPh.D.
Carbonic anhydrases (CAs, EC 4.2.1.1) are a class of metalloenzymes that catalyze the hydration of CO2 under physiologic conditions and are involved in many physiological and pathological processes. Modulation of CA activity, particularly CA inhibition is exploited pharmacologically for the treatment of many diseases such as cancer, glaucoma, edemas, mountain sickness. CA activation has been less frequently investigated till recently. Genetic deficiencies of several CA isozymes are reported in the literature and reflect the important role of carbonic anhydrases in human physiology and homeostasis. Activation of CA isozymes in brain have been correlated recently with spatial learning and memory. Based on these premises, activators of CA isozymes have the potential to alleviate mild dementias and to act as potential nootropic agents. In chapter 3, continuing our long-term interests towards the development of potent and selective CAAs, we carried out X-ray crystallographic studies with a small series of pyridinium histamine derivatives, previously developed as CAAs by our group. This study revealed important insights into the binding of this class of activators into the active site of CA II isozyme. A potent pyridinium histamine CAA 25i was successfully crystallized with CA II isozyme and was found to bind into the hydrophobic region of the active site, with two binding conformations being observed. This is one of the very few X-ray crystal structures of a CAA available. Based on the findings of this X-ray crystallographic study and building on our previously developed ethylene bis-imidazole CAAs, we advanced a novel series of lipophilic bis-imidazoles. Enzymatic assays carried out on purified human CA isozymes revealed several low nanomolar potent activators against various brain-relevant CA isozymes. Bis-imidazole 30e was found to be a nanomolar potent activator for CA IV, CA VA and CA IX. Due to their conjugated structure, these CAAs were also fluorescent and therefore were fully characterized in terms of photophysical properties, with several representatives proving to display very good fluorophores. The very good activation profile against several different CA isozymes, along with excellent fluorescence properties recommend these compounds as great molecular tools for elucidation of role of CA isozymes in brain physiology, as well as towards improvement of memory and learning. Focusing on inhibition of CA isozymes, it must be stressed that over the last decade a clear connection had been established between the expression of CA IX and CA XII and cancer. Since cancer is the second most common cause of death in the world, we explored the possibility to kill cancer cells via inhibition of different CA isozymes present in cancer cells. The membrane bound carbonic anhydrase IX (CA IX) isozyme represents a particularly interesting anticancer target as it is significantly overexpressed in many solid tumors as compared to normal tissues. In malign tissues this CA isozyme was found to play important role in pH homeostasis and promotes tumor cell survival, progression and metastasis. Thus, CA IX represents a potential biomarker and an appealing therapeutic target for the detection and treatment of cancer. CA IX can be targeted either through the development of small or large molecular weight, potent, and selective inhibitors or through the development of CA IX targeted drug delivery systems for selective delivery of potent chemotherapeutic agents. Building on these premises, in this dissertation, we also revealed our continuing efforts towards the development of potent and selective CA IX inhibitors along with their translation into the development of CA IX targeted drug delivery systems. In chapter 4, we designed a series of small molecular weight (MW) ureido 1,3,4-thiadiazole sulfonamide derivatives employing the “tail approach”, through the decoration of established sulfonamide CA inhibitor warheads with different tail moieties via ureido linker. The generated CAIs were tested against tumor associated CA IX and CA XII isozymes and off-target cytosolic isozymes CA I and CA II, and were revealed to be moderate to highly selective and nanomolar, even sub-nanomolar, potent CA IX inhibitors. Several potent pan-inhibitors were also identified in this section. We assessed these CAIs for their in vitro cell killing ability using MDA-MB 231 breast cancer cell line expressing CA IX and CA XII. The most efficient CAI proved to be ureido-1,3,4-thiadiazole-2-sulfonamide 69, which showed subnanomolar potency against purified human CA IX and CA XII isozymes, with good selectivity against CA I and CA II, and consistent, statistically significant cancer cell killing. In Chapter 5, continuing our efforts towards the development of potent and selective CA IX inhibitors, we designed, synthesized, characterized and evaluated a new series of PEGylated 1,3,4-thiadiazole-2-sulfonamide CAIs, bearing different PEG backbone length. We increased the PEG size from 1K to 20K, in order to better understand the impact of the PEG linker length on the in vitro cell killing ability against CA IX expressing cancer cell lines and also against a CA IX negative cell line. In vitro cell viability assays revealed the optimum PEG linker length for this type of bifunctional bis-sulfonamide CAIs in killing the tumor cells. The most efficient PEGylated CAI was found to bis-sulfonamide DTP1K 91, which showed consistent and significant cancer cell killing at concentrations of 10−100 μM across different CA IX and CA XII expressing cancer cell lines. DTP1K 91 did not affect the cell viability of CA IX negative NCI-H23 tumor cells, thus revealing a CA IX mediated cell killing for these inhibitors. In chapter 6, we decided to further explore the possibility of using CA IX as a targeting epitome for the development of a gold nanoparticle-based drug delivery system. We translated the oligoEG- and PEGylated CAI conjugates into efficient targeting ligands for gold nanoparticle decoration along with chemotherapeutic agent doxorubicin (Dox), in a novel multi-ligand gold nanoplatform designed to selectively release the drug intracellularly, in order to enhance the selective tumor drug uptake and tumor killing. We were successful in developing compatible CAI- and Dox- ligands for efficient dual functionalization of gold nanoparticles. Our optimized, CA IX targeted gold nanoplatform was found to be very efficient towards killing HT-29 tumor cells especially under hypoxic conditions, reducing the hypoxia-induced chemoresistance, thus confirmed the potentiating role of CA IX as a targeting epitome.
Temple University--Theses
ATZORI, ELENA. "Molecular studies in the human salivary protein carbonic anhydrase VI." Doctoral thesis, Università degli Studi di Cagliari, 2014. http://hdl.handle.net/11584/266513.
Повний текст джерелаLiu, X. "Investigating the effects of human Carbonic Anhydrase 1 expression in mammalian cells." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3001586/.
Повний текст джерелаUdd, Annika. "The interaction of human carbonic anhydrase II to solid surfaces and its applications." Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-19088.
Повний текст джерелаThe adsorption of proteins to solid surfaces has been extensively investigated during the past 20-30 years. The knowledge can be applied in biotechnological applications in for example immunoassays and biosensors. Human carbonic anhydrase II is a widely studied protein and the CO2-activity makes it an interesting candidate for biotechnological purposes. To make this possible, the factors affecting the adsorption of proteins have to be mapped. The stability of the protein is under great influence of the adsorption and the protein tends to undergo conformational changes leading to a molten globule like state upon adsorption. The stability of a protein also affects the extent of conformational changes and the nature of the adsorption. A more stable protein, adsorbs with less structural changes as a consequence of adsorption, and desorbs from the surface more rapidly than a less stable one. Also the hydrophobicity, charge and area of the surface are affecting the interaction with the protein. Still, the same adsorption pattern is noticed for the same protein at different surfaces, leading to the conclusion that the properties of the protein affect the interaction, rather than the properties of the surface. Biosensors containing carbonic anhydrase have been developed. These make measurement and detection of zinc ions possible. To be able to use carbonic anhydrase as a potential agent in biotechnology, attached to solid surfaces, the protein has to be biotechnologically engineered to get a more stable structure, or else the denaturation will destroy this possibility.
Almstedt, Karin. "Protein Misfolding in Human Diseases." Doctoral thesis, Linköpings universitet, Biokemi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-21077.
Повний текст джерелаKivelä, J. (Jyrki). "Human salivary carbonic anhydrase isoenzyme VI:physiology and association with the experience of dental caries." Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514251407.
Повний текст джерелаKarabencheva-Christova, Tatyana G., Uno Carlsson, Kia Balali-Mood, Gary W. Black, and Christo Z. Christov. "Conformational Effects on the Circular Dichroism of Human Carbonic Anhydrase II : A Multilevel Computational Study." Linköpings universitet, Institutionen för fysik, kemi och biologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-92709.
Повний текст джерелаFunding Agencies|UK National Service for Computational Chemistry Software||UK National Supercomputer Service Hector||Marie Curie Fellowships (FP7 of EU)||
Baranauskienė, Lina. "Analysis of ligand binding to recombinant human carbonic anhydrases I, II, VII, IX and XIII." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2013~D_20130327_100539-96804.
Повний текст джерелаKarboanhidrazės (CA) yra metalofermentai, katalizuojantys virsmus tarp anglies dioksido ir bikarbonato. Jų slopinimas gali būti taikomas gydyti tokias skirtingas ligas kaip glaukoma, vėžys, nutukimas, epilepsija, osteoporozė ir kt. Šiuo metu yra beveik 30 mažamolekulinių junginių, kurie naudojami kaip vaistai, su padidėjusiu karboanhidrazių aktyvumu susijusioms ligoms gydyti. Darbe tirta rekombinantinių žmogaus karboanhidrazių I, II, VII, IX ir XIII sąveika su sulfonamidiniais ligandais. Įvertintas tirtų baltymų stabilumas skirtingomis eksperimentinėmis sąlygomis, nustatyta priešvėžinio taikinio CA IX oligomerinė būsena. Modeliniais baltymais naudojant karboanhidrazes, praplėstos terminio poslinkio metodo taikymo ribos. Išmatuoti 40 naujų susintetintų junginių sąveikos su karboanhidrazėmis termodinaminiai parametrai, išanalizuota CA XIII sąveikos su sulfonamidiniais slopikliais termodinamika, atskiriant tikruosius, nuo eksperimento sąlygų ir susijusių reakcijų nepriklausančius jungimosi parametrus.
Yang, Jie. "Development of Peptide Binders : Applied to Human CRP, Carbonic Anhydrase (II, IX) and Lysine Demethylase 1." Doctoral thesis, Uppsala universitet, Institutionen för kemi - BMC, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-330489.
Повний текст джерелаGlöckner, Steffen [Verfasser], and Klebe [Akademischer Betreuer]. "Thermodynamic, Kinetic and Crystallographic Investigations of Benzenesulfonamides as Ligands of Human Carbonic Anhydrase II / Steffen Glöckner ; Betreuer: Klebe." Marburg : Philipps-Universität Marburg, 2020. http://d-nb.info/1224046749/34.
Повний текст джерелаMorssing, Vilén Eric. "Studies of Disulfide Bridge Formation in Human Carbonic Anhydrase Between Engineered Cysteines in Non Ideal Conformations Under Equilibrium and Kinetic Conditions." Thesis, Linköping University, The Department of Physics, Chemistry and Biology, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-9120.
Повний текст джерелаStabilization of proteins is of great interest for the biotechnological society, industrial as well as research areas. Proteins with high stability are more suitable as reagents, easier to handle, store, transport and use in industrial processes. One way to stabilize a protein is to introduce a disulfide bridge into the structure by protein engineering. In this report the formation of a disulfide bridge between engineered cysteines in non ideal conformations in human carbonic anhydrase has been investigated. The disulfide bridge is not formed when the protein is in its native state. It is shown that when the protein is exposed to mild concentrations of urea in the presence of DTTox the disulfide bridge is formed. Also upon refolding in vitro, in a non oxidative environment, disulfide bridges are formed. This observation is worth to notice, since the disulfide bridge does not form to any appreciable extent when the protein is expressed and folded in vivo in Escherichia coli.
Buratto, Jeremie. "Reconnaissance de surfaces protéiques par des foldamères d'oligoamides aromatiques." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0003/document.
Повний текст джерелаProtein-protein interactions are a central issue in biological processes and represent relevant therapeutic targets for the treatment of diseases. The design of antagonistic molecules directed towards the disruption of these interactions requires the specific recognition of protein surfaces. Quinoline oligoamide foldamers present all the properties to reach that point. They are easily synthesized and fold into helices (similar to α helices) which can be decorated. Thanks to biophysical studies (CD, SPR, RX diffraction), we demonstrate that these molecules are able to recognize protein surfaces. Two proteins have been studied: the human interleukin 4 and the human carbonic anhydrase II.The applied strategy (keeping the foldamer close to the protein surface via a linker) allowed us to gather structural information about foldamer protein interactions before any strong binding is established. The first crystal structure between a protein and an aromatic amide foldamer is reported
Vallade, Maëlle. "Reconnaissance de surfaces de protéines par les foldamères d'oligoamides aromatiques." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0145/document.
Повний текст джерелаSince proteins are at the basis of many biological processes, they are widely studied as therapeutic targets. Aromatic oligoamide foldamers have a very well defined structure, predictable and stable both in solution and solid state. Because of their medium size, they appear as potent candidates for protein surface recognition thanks to their proteinogenic side chains. This manuscript presents the different steps of their design, from the scaffold’s synthesis to obtaining a functionalized foldamer, thanks to solid phase synthesis. The strategy to investigate protein/foldamer interactions will be detailed. Its originality lies in the fact that the foldamer is anchored to the protein. Circular dichroism has been used as a screening method to detect foldamer/protein interactions. Structural analysis of the hits will allow the design of new foldamers with the objective of enhancing foldamer/protein interactions: it is an iterative strategy. This approach has been applied firstly to human carbonic anhydrase II (HCA). This protein is used as a model system and proof of concept before moving to more therapeutically relevant proteins; interleukin 4 and cyclophilin A. Finally, a study on introducing flexibility in quinoline foldamers is presented
Köhn, Linda. "Genetic mapping of retinal degenerations in Northern Sweden." Umeå : Umeå university, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-27004.
Повний текст джерелаKim, Junseok. "Bioanalytical Applications of Intramolecular H-Complexes of Near Infrared Bis(Heptamethine Cyanine) Dyes." Digital Archive @ GSU, 2008. http://digitalarchive.gsu.edu/chemistry_diss/23.
Повний текст джерелаWilkinson, Brendan Luke. "Synthesis of Novel Carbohydrate Based Enzyme Inhibitor Libraries Utilising Click Chemistry." Thesis, Griffith University, 2007. http://hdl.handle.net/10072/366473.
Повний текст джерелаThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Full Text
Teruya, Kanae. "Development of Affinity-Based Chemical Probes for Fluorescence Detection of Human Carbonic Anhydrases." Thesis, Griffith University, 2016. http://hdl.handle.net/10072/367357.
Повний текст джерелаThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
Full Text
Paul, Blessy Abraham. "Structure-Based Drug Design for Carbonic Anhydrases & Membrane Interactions of Human Visinin-Like Protein-1 (VILIP-1)." Thesis, Griffith University, 2011. http://hdl.handle.net/10072/366481.
Повний текст джерелаThesis (Masters)
Master of Philosophy (MPhil)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
Full Text
Tollstoy, Tegler Lotta. "Polypeptide Conjugates as High-affinity Binders for Proteins." Doctoral thesis, Uppsala universitet, Institutionen för biokemi och organisk kemi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-101406.
Повний текст джерелаCanela, Heliara Maria Spina. "Análise molecular da anidrase carbônica no fungo patogênico humano Aspergillus fumigatus." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-29012014-091548/.
Повний текст джерелаThe fungus Aspergillus fumigatus is the second cause of fungal infections in immunocompromised patients and it is the main specie which causes invasive aspergillosis, a disease with high mortality rate that mainly affects the lungs and it can spread through the body. During the infectious process, the fungus must adapt to the host and one of the obstacles is the drastic change of the carbon dioxide (CO2) concentration, which is 0.033% in the environment and until 6% inside the host. The carbonic anhydrases are enzymes which are involved in the reversible hydration of carbon dioxide and they have been pointed as important in the virulence of pathogens such as Plasmodium falciparum, Mycobacterium tuberculosis, Helicobacter pylori, Cryptococcus neoformans and Candida albicans. This work aimed to evaluate the role of the enzyme carbonic anhydrase in the development and virulence of the fungus A. fumigatus, which has four homologues of this enzyme (cafA, cafB, cafC e cafD). Therefore, strains, which have the homologues of the enzyme deleted (?cafA, ?cafB, ?cafC, ?cafD and ?cafA?cafB) were used in parallel with the wild strain (?akuBku80), which originated the mutant ones. We did structure phenotypic evaluations of the different strains of conidiophores, sensibility determination against different stressors (antifungal agents, apoptosis, ionic, nitrosative, oxidative, and cell wall stress promoters) and global gene expression determination at different carbon dioxide concentrations. It was verified that the carbonic anhydrases homologues deletion of A. fumigatus did not interfere on the n structure (conidiophore) of this fungus, in the tested conditions. On the other hand, the deletion caused a change in sensibility of the fungus against some stressors (acetic acid and hydrogen peroxide). The gene expression experiments showed a gene involved in the adaptation to the increase of CO2 concentration, the cipC gene. This gene does not have homologues in the mammalian cells. The cipC gene was characterized in this work by its deletion in the A. fumigatus wild strain (?akuBku80) and microscopic phenotypic evaluation and sensibility tests against stressors (antifungal agents, apoptosis, ionic, nitrosative, oxidative, and cell wall stress promoters). The gene deletion did not interfere on the fungus conidiophore structure but increase its sensibility to some compounds (calcoflúor white and menadione). Virulence tests in animal model using the ?cipC mutant were done and they showed that the deletion of this gene attenuates the fungus virulence. In conclusion, the carbonic anhydrases are not relevant to development and virulence of the fungus, which modifies the gene expression to adapt to the variations of atmospheric CO2 concentration. Besides, the cipC gene seems to be involved in this adaptation process. Moreover, the cipC gene showed to be important to the development of the fungus and its virulence, which makes the gene a target for the study of new therapies for the treatment of invasive aspergillosis.
Berrino, Emanuela, Claudiu Supuran, Alessandro Mugelli, and Fabrizio Carta. "Carbonic Anhydrase Inhibitors: Versatile Agents for the Treatment of Human Diseases." Doctoral thesis, 2020. http://hdl.handle.net/2158/1188882.
Повний текст джерелаandrea, angeli. "Synthesis, characterization, biological assays and development of new enzyme modulators for the treatment of human pathologies." Doctoral thesis, 2019. http://hdl.handle.net/2158/1150779.
Повний текст джерелаDai, Huei-Yue, and 戴惠玉. "Carbonic anhydrase III enhances transformation and invasion capablity in human hepatocellular carcinomas." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/08689843117252880115.
Повний текст джерела國防醫學院
生命科學研究所
96
Carbonic anhydrase III (CAIII) is distinguished from the other members of the CA family by low carbon dioxide hydratase activity, resistance to the CA inhibitor acetazolamide, and a predominant expression in the liver of males. In our animal study, the CAIII expression was over-expressed in the foci of altered hepatocytes (FAH) and was consistently down-regulated in hepatocellular carcinoma. We also found that the expression of CAIII was slightly increased in early stage of most HCC (63%), but it became significantly weaker in late stages of HCC. Ectopic overexpression of CAIII in SK-Hep1 cells resulted in increased anchorage-independent growth and invasiveness. Compared with the control animals, the metastasis nodules of lung increased in the population of pooled CAIII transfectants. And siRNA-mediated silencing of CAIII expression decreased the invasive ability of SK-Hep1 cells. Furthermore, CAIII transfectants showed elevated focal adhesion kinase (FAK), Src activity and MMP-3 protein expression. Silencing of FAK expression in CAIII transfectants led to suppression of HCC cell invasion. More importantly, the CAIII transfectants acidified the culture medium at an accelerated speed than the control cells did. Intracellular pH, determined by pH-sensitive bis-carboxyethyl-carboxyfluorescein (BCECF) probe, was lower in CAIII transfectant cells than vector only control cells. The number of migrated and invasive cells was significantly increased in cultured medium of pH 6.8 than that in pH 7.4 condition. Western blot also showed that SK-Hep1 cells cultured at pH 6.8 had higher phospho-FAK, phospho-Rac-1/cdc42 and vimentin expression than that at pH 7.4. Base on these results, we suggest that the CAIII-promoted invasive ability of HCC cells may probably be mediated through, at least in part, the FAK signaling pathway via intracellular and/or extracellular acidification.
Wu-Hsien and 郭武憲. "The differential expression of cytosolic carbonic anhydrase in human hepatocellular and breast carcinoma." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/72360866897941674111.
Повний текст джерела中山醫學大學
生化暨生物科技研究所
94
Cytosolic carbonic anhydrases (CAs), including CAI, CAII and CAIII are presented in normal hepatocytes. This study was aimed to investigate the expression status of CAs in hepatocellular carcinomas (HCC) and breast cancer and the role of tumor progression. The activity, protein expression pattern and messenger RNA of cytosolic CA were analyzed by CA activity analysis, Western blotting and RT-PCR in 60 human hepatocellular carcinomas and 60 human breast cancer surgical specimens. The result shows that in each of 60 HCC, CA activity and protein expression in tumor area is significantly lower than that of paired adjacent normal tissues (P<0.01), and mRNA expressions in tumor areas are also reduced (P<0.001). Furthermore, the immunohistochemical studies have further confirmed this reduction of CAI, CAII and CAIII protein expression in tumor areas. There is a statistically significant reduction in the expression of cytosolic CAII in poorly differentiated cancer (P < 0.001). Furthermore, in 60 breast cancer patients, the result showed that CA activity and CA II protein expression in tumor area was significantly higher than that of paired adjacent normal tissues (P < 0.01), while the CA I and CA III protein expression was lower (P < 0.001). Furthermore, further linear regression analysis has showed that the tumor size positively correlated with CA activity in tumor tissue samples (R=0.48, P<0.05). In addition, further statistical analysis for clinic pathological parameters revealed that CA activity was significantly increased in patients with metastasis (P <0.05). CA activity in tumor tissue might reflect the severity of invasion of breast cancer and various CA inhibitors might be selectively used as potential anti-metastasis agents according to tumor size.
MALANHO, DA SILVA JOSE PEDRO. "Ultra-high resolution structure determination of transition metal substituted human carbonic anhydrase 2 – inhibitor complexes." Doctoral thesis, 2022. https://hdl.handle.net/2158/1291044.
Повний текст джерелаLo, Che-Min, and 駱哲民. "The Promoter Analysis and Transcriptional Regulation of Human Carbonic Anhydrase VIII (hCAVIII) Gene in a MERRF Disease Model." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/n8a428.
Повний текст джерелаBRUNO, ELVIRA. "Probing the molecular interactions between human Carbonic Anhydrases (hCAs) and a novel class of designed benzenesulfonamides." Doctoral thesis, 2017. http://hdl.handle.net/11570/3103414.
Повний текст джерелаROTONDI, GIULIA. "Development of novel inhibitors targeting the tumour-related carbonic anhydrase isoforms and of small molecule ligands targeting the human tyrosinase and tyrosinase related protein 1." Doctoral thesis, 2020. http://hdl.handle.net/11573/1470297.
Повний текст джерелаLin, Yung-Lun, та 林永倫. "一.Synthesis and Kinetic Study of Quinoxalinone-Based Sulfonamides as New Human Erythrocyte Carbonic Anhydrase II Inhibitors二.The Applications of [b-3C-im][NTf2] Ionic Liquid in Claisen rearrangement Reaction". Thesis, 2007. http://ndltd.ncl.edu.tw/handle/78031405060100864080.
Повний текст джерела國立中正大學
化學所
95
Carbonic anhydrase (CA) is a zinc-containing metalloenzyme that is widespread in nature and catalyzes the reversible hydration of CO2 to HCO3- and H+. CA is expressed in a number of isoforms (CA I-XIV) with varying degrees of enzymatic activity and participates in various physiological/pathological processes in human body. Inhibition of the zinc metalloenzyme human CAII by sulfonamides has the potential to treat clinically important diseases such as glaucoma, osteoporosis and most recently cancers. In this study, a new class of human CAII inhibitors with conformationally constrained core structure was designed to increase its binding affinity. Totally, Sixteen quinoxalinone-based sulfonamide inhibitors were synthesized in 2~3 steps with the total isolated yields of 5-89%. The activity (Ki) of these inhibitors toward human CAII were screened spectrometrically and determined by the Lineweaver-Burk plots. The inhibition constants obtained were in the range of 370-8200 nM. In this study, the conformationally constrained inhibitors were demonstrated to be more potent in the inhibition of human CAII, as compared to the conformationally relaxed inhibitors. In addition, the rigidity of the fused aromatic ring appears to play important role in enzymatic inhibition. Ionic liquids are solvents systems that consist of cation and anions at ambient temperature. We previously reported the new ionic liquid, [b-3-C-im][NTf2], which is not only chemically stable, but also has a low melting point, low water content and dynamic viscosity. In this work, this new ionic liquid was applied to the Claisen rearrangement reaction,in conjunction with focused microwaves. Under the optimized conditions, the Claisen rearrangement reaction was achieved in 3 minutes. Moreover, the Lewis acid (MgCl2) was introduced to decrease the reaction temperature (250℃→200℃) successfully, and with good overall isolated yield.
Ming-Ju and 謝明儒. "Part I: The inhibition of migration and invasion in human breast cancer cells by carbonic anhydrase II, IX and XII RNA interferencePart II: Molecular mechanism of hepatitis C virus E2-induced hepatic fibrosis." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/11789935411087098767.
Повний текст джерела中山醫學大學
生化暨生物科技研究所
99
Part: I Carbonic anhydrase (CA) is an enzyme with zinc metal ions, including a number of different isoforms, and its main function lies within the catalytic acid cells and maintain the cell''s internal balance. CA II, CA IX and CA XII are considered to affect the cell''s internal balance of carbonate ions and maintain the normal extracellular pH. A previous study conducted with 60 breast cancer patients revealed a significant increase of CA II protein expression and CA activity in in tumor (P <0.001), as well as mRNA and protein expression levels. Furthermore, a significant correlation was found between CA II activity and tumor size while CA IX and CA XII are involved in the process of tumor development. Although there were extensive results indicating the involvement of CA II and CA IX in the cancer cell invasion and migration, similar studies for CA XII is less and insufficient. Previous studies have revealed that CA XII expression is an indicator for breast cancer cell invasion and useful for tracking surgical outcomes. Therefore, the aim of this study was to explore the impact of CA II, CA IX and CA XII on the extent of invasion and mobility in different breast cancer cells. Furthermore, the related pathways were alsoexplored. In the study with breast cancer cells of different levels of invasion and mobility, results from RNA interference technology showed that the CA XII RNA interference has the most significant inhibition capability for the invasion and migration of MDA-MB-231 cells. Further studies revealed that such inhibition is via an inhibition of phosphorylation of p38. In the final in vivo experiments, CA XII-knockdown MDA-MB-231 cells were inoculated into mice to show that the tumor size and animal body weight were significantly reduced in CA XII-knockdown mice. Take together, these results confirmed that CA XII indeed play an important role in the invasion and migration of MDA-MB-231 breast cancer cells. Part: II Chronic infection of hepatitis C virus (HCV) leads to hepatic fibrosis and subsequently cirrhosis, although the underlying mechanisms have not been established. Previous studies have indicated that the binding of HCV E2 protein and CD81 on the surface of hepatic stellate cells (HSCs) lead to the increased protein level and activity of matrix metallopeptidase (MMP) 2, indicating that E2 may involve in the HCV-induced fibrosis. This study was designed to investigate the involvement of HCV E2 protein in the hepatic fibrogenesis. Results showed that E2 protein may promote the expression levels of α-smooth muscle actin (α-SMA) and collagen α(I). Furthermore, several pro-fibrosis or pro-inflammatory cytokines, including transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), interleukin (IL)-6 and IL-1β, were significantly increased in E2 transfected-HSC cell lines, while the expression of MMP-2 are also considerably increased. Moreover, the significant increases of CTGF and TGF-β1 in a stable E2-expressing Huh7 cell line were also observed the same results. Further molecular studies indicated that the impact of E2 protein on collagen production related to higher production of ROS and activated Janus kinase (JAK)1, JAK2 and also enhance the activation of ERK1/2 and p38, while catalase and inhibitors specific for JAK, ERK1/2, and p38 abolish E2-enhanced expression of collagen α(I). Taken together, this study indicated that E2 protein involve in the pathogenesis of HCV-mediated fibrosis via an up-regulation of collagen α(I) and oxidative stress, which is JAK pathway related.
Truppo, Emanuela. "BIOCHEMICAL AND STRUCTURAL CHARACTERIZATION OF HUMAN CARBONIC ANHYDRASES." Tesi di dottorato, 2011. http://www.fedoa.unina.it/8812/1/Truppo.pdf.
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