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Tesi sul tema "Enzymes Synthesis"

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Autore: Grafiati

Pubblicato: 4 giugno 2021

Ultima modifica: 6 settembre 2023

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1

Ekici, Özlem Doğan. "Design, synthesis, and evaluation of novel irreversible inhibitors for caspases". Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04062004-164633/unrestricted/ekici%5Fozlem%5Fd%5F200312%5Fphd.pdf.

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2

Ekici, Ozlem Dogan. "Design, synthesis, and evaluation of novel irreversible inhibitors for caspases". Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/5333.

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3

Naylor, Neil J. "Biotransformations involving hydrolytic enzymes". Thesis, University of Warwick, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263607.

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4

Silveira, Alvito J. "Synthesis of 6-guanidinobenzoxazinones as potential inhibitors of trypsin-like enzymes". Thesis, Georgia Institute of Technology, 1989. http://hdl.handle.net/1853/26914.

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5

Snider, Catherine E. "Synthesis and biochemical evaluation of irreversible inhibitors of aromatase /". The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487266362338344.

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6

Carnell, Andrew John. "Cycloalkanone monooxygenase enzymes in organic synthesis". Thesis, University of Exeter, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293971.

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7

Blum, Janna Karen. "Broadening the enyzme-catalyzed synthesis of semi-synthetic antibiotics". Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39528.

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Abstract (sommario):

An alpha-amino ester hydrolase (AEH) applicable to synthesis of semi-synthetic antibiotics was cloned from the genomic DNA of Xanthomonas campestris pv. campestris sp. strain ATCC 33913. AEHs catalyze the synthesis and hydrolysis of alpha-amino beta-lactam antibiotics. The enzyme was characterized for thermodynamic and kinetic parameters. The enzyme shows optimal ampicillin hydrolytic activity at 25C and pH 6.8. The AEH enzymes have been shown to have excellent synthetic capability. Additionally, we demonstrated the first fully aqueous enzymatic one-pot synthesis of ampicillin direct from the natural product penicillin G eliminating the isolation of the intermediate 6-APA. Lastly, to improve the thermostability of the AEH a modified structure-guided consensus model of seven homologous enzymes was generated along with analysis of the B-factors from the available crystal structures of the known AEH from Xanthomonas citri. Our best variant, which is a quadruple mutant, E143H/A275P/N186D/V622I, which has a T_50_30, the temperature at which the half-life is 30 minutes, of 34C and 1.3-fold activity compared to wild-type. Overall, we have successfully improved the understanding of the AEH class of enzymes and applied a novel cascade application, demonstrating AEHs unique applicability in the synthesis of beta-lactam antibiotics. The improved thermostability will further improve the industrial relevance of AEHs.

8

Admans, Gary David. "Asymmetric transformations catalysed by lipase enzymes". Thesis, University of Exeter, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240288.

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9

Chambers, Martina Natasha. "Synthesis of cellulosic glycolipids using engineered enzymes". Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/46032.

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Cellulose, a linear polymer of D-glucose units connected by β-1,4 glycosidic bonds, adopts a highly-ordered crystalline structure in solution. In cellulose I, the dominant form of cellulose in nature, the polymeric chains are aligned in the same direction. Previous attempts to synthesize cellulose I in vitro have resulted in the synthesis of cellulose II, which has the thermodynamically favored anti-parallel orientation of chains. The synthesis of soluble fragments or defined surfaces of cellulose I would enable more detailed study of carbohydrate binding domains and other proteins that interact with cellulose in nature. The objective of this thesis is to prepare a crystalline surface of cellulose I in a controlled manner through the alignment of cellulolipids. A major focus of this thesis is the synthesis of cellulolipids with a cellohexaosyl head group. Cellohexaose is the shortest cello-oligosaccharide with cellulosic properties, but is consequently insoluble in aqueous solution. To improve the solubility of cellohexaose, the addition of a removable charged functionality was explored: either a terminal sialic acid or a phosphate group at the 6 position of the non-reducing terminal glucose. Abg2F6 glycosynthase from Agrobacterium sp. was used to synthesize β-1,4 linked cello-oligosaccharide fluorides from DP = 2 to DP = 4. These cello-oligosaccharides were modified with a removable charged functionality and utilized as donor substrates by CelB glycosynthase, a mutant of a β-1,4 endoglucanase from Caldicellulosiruptor saccharolyticus. Through the combination of glycosynthase enzymes and charged functionalities, a variety of soluble cellohexaosyl analogs were synthesized. Lyso-glycosphingolipids were prepared by transferring cello-oligosaccharyl fluorides to D-erythro-C18-sphingosine using EGCase glycosynthase. CelB glycosynthase used charged glycosyl fluoride donors to extend the lyso-glycosphingolipids, yielding soluble cellulolipids. The soluble cellulolipids were aligned along an aqueous:organic interface and the charged functionality was removed. Thus, a surface was prepared that appeared to interact with a carbohydrate binding module functionalized with a fluorescent tag. The soluble cellulolipids were successfully incorporated into a nanodisc, as shown through the incorporation of phosphorylated cellohexaosyl sphingosine. Cleavage of the phosphate using alkaline phosphatase yielded a nanodisc containing cellulolipids.

10

Ahmed, Naveed. "The synthesis of inhibitors of proteolytic enzymes". Thesis, University of Huddersfield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416765.

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11

Davis, Benjamin G. "Synthesis of inhibitors of sugar processing enzymes". Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711593.

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12

Dotse, Anthony Kwabla. "Design, synthesis and evaluation of novel inhibitors of cysteine proteases, metalloproteases and the proteasome, a unique high molecular weight proteolytic enzyme". Diss., Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/29979.

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13

Parekh, Parag A. "Bioprocess development for asymmetric reductions by Saccharomyces cerevisiae enzymes". [Gainesville, Fla.] : University of Florida, 2006. http://purl.fcla.edu/fcla/etd/UFE0014371.

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14

Qiu, Jian. "Synthesis of inhibitors of terpene and shikimate enzymes". Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627500.

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15

Guilly, Selena. "Synthesis of novel acceptor substrates for glycosyltransferase enzymes". Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/16997.

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Abstract (sommario):

Our research has been based on the biosynthetic pathway to N-linked glycoproteins, species which are comprised of an oligosaccharide moiety attached to the side-chain nitrogen atom of an asparagines residue in a peptide. In order to effectively study the steps involved in the biosynthesis of lipid-linked oligosaccharides and their subsequent transfer to a nascent protein in cotranslational modification processes, it is essential to have a source of pure dolichols in quantities sufficient to allow the synthesis of both biosynthetic intermediates and synthetic analogues in the pathways responsible for the biogenesis of glycoproteins. Since supplies of naturally occurring dolichols are scarce and they are difficult to synthesise, a number of lipid substrates were prepared as synthetic analogues of naturally occurring dolichyl phosphate. (Fig. 6302A) The synthesis and biological testing of lipids 1 and 2 are reported. The result of a study of the fluorescence of lipid 1 is also presented. Work towards the preparation of lipid 3 is detailed. Many of the enzymes involved in the biosynthesis of N-linked glycoproteins have already been isolated and characterised, however, some of those enzymes involved in the early stages of N-glycan biosynthesis remain unidentified. In order to gain more information about the unknown mannosyltransferases that are active in the early stages of N-glycan biosynthesis, a phytanyl-linked monosaccharide (glucosamine), 4, and disaccharide (chitobiose), 5, were prepared. (Fig. 6302B) The syntheses of chitobiose phosphate from commercially available chitobiose octaacetate is reported. Details of the preparation of N-acetyl glucosaminyl phosphate from commercially available N-acetyl glucosamine are pretend. The lipid moiety, phytanyl phosphate, was derived from commercially available phytol. The manner in which phytanyl phosphate was coupled to both the monosaccharide phosphate and the disaccharide phosphoryl species is detailed and results of subsequent biological testing are reported. Finally, work towards the preparation of a fluorescently-labelled asparagine-linked chitobiosyl substrate, 6, is reported.

16

Mazda, Xerxes Cyrus. "Synthesis of substrate analogues for terpene cyclase enzymes". Thesis, University of Cambridge, 1992. https://www.repository.cam.ac.uk/handle/1810/272667.

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17

Holt, Karen Elizabeth. "Asymmetric synthesis of aza-sugars using aldolase enzymes". Thesis, University of Cambridge, 1993. https://www.repository.cam.ac.uk/handle/1810/272658.

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18

Vázquez-Figueroa, Eduardo. "Development of a novel dehydrogenase and a stable cofactor regeneration system". Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/31685.

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Abstract (sommario):

Thesis (Ph.D)--Chemical Engineering, Georgia Institute of Technology, 2009.
Committee Chair: Bommarius, Andreas S.; Committee Member: Doyle, Donald F.; Committee Member: Koros, William J.; Committee Member: Moore, Jeffre C.; Committee Member: Prausnitz, Mark R. Part of the SMARTech Electronic Thesis and Dissertation Collection.

19

Heng, Sabrina. "The Design, Synthesis and Characterization of Enzyme Inhibitors". Thesis, Boston College, 2009. http://hdl.handle.net/2345/755.

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Thesis advisor: Evan R. Kantrowitz
Thesis advisor: Mary F. Roberts
In this work, a series of inhibitors of two enzymes, aspartate transcarbamoylase (ATCase) and fructose 1,6-bisphosphatase (FBPase) were designed, synthesized and characterized. ATCase catalyzes the committed step in pyrimidine nucleotide biosynthesis, the reaction between carbamoyl phosphate (CP) and L-aspartate to form N-carbamoyl-L-aspartate (CA) and inorganic phosphate. This step is exceptionally important because once CA is formed, it is committed to the biosynthesis of pyrimidines, a necessary component for nucleic acid biosynthesis. The pyrimidine biosynthetic pathway plays an important regulatory role in cell proliferation since there is evidence that intracellular nucleotide pools control DNA replication and consequently cell division. Thus, the enzymes of pyrimidine biosynthesis, both in the de novo and salvage pathways, are targets for anti-proliferation drugs. Fructose 1,6-bisphosphatase (FBPase) is responsible for the hydrolysis of fructose 1,6-bisphosphate (F16BP) to fructose 6-phosphate (F6P). As the key enzyme at the control point in the gluconeogenesis pathway, FBPase presents an opportunity for the development of novel inhibitors against type-2 diabetes aimed at lowering the hepatic glucose production in type-2 diabetes. With ATCase, the design, synthesis and characterization of (1) T-state inhibitors composed of two phosphonacetamide groups linked together by a variety of functionalities and (2) analogs of N-phosphonacetyl-L-aspartate, a potent inhibitor of ATCase, were accomplished. With FBPase, a library of allosteric inhibitors, of which, the lead compound was initially identified through a virtual high-throughput screening system, was developed. In addition, this work also aimed to find the in vivo target for achyrofuran, a natural product derived from Achyrocline satureoides which has been shown to significantly lower blood glucose levels in db/db mouse for type-2 diabetes. The last project presents evidences that FBPase is the likely in vivo target for achyrofuran. This was accomplished through the use of computational docking experiments and by the synthesis of a new class of inhibitors based on the achyrofuran scaffold
Thesis (PhD) — Boston College, 2009
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

20

Hinchliffe, Paul Stuart. "The synthesis of #beta#-sultam inhibitors of proteolytic enzymes". Thesis, University of Huddersfield, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368328.

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21

Bingham, Matilda Jane. "Insights into the design and synthesis of artificial enzymes". Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395525.

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22

Lemoult, Stephanie Claudette. "Biocatalysis in organic synthesis using microorganisms and immobilised enzymes". Thesis, University of Exeter, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260622.

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23

Newgas, Sophie Alice. "Biocatalysis using plant and metagenomic enzymes for organic synthesis". Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10052003/.

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Biocatalysts provide an excellent alternative to traditional organic chemistry strategies, with advantages such as mild reaction conditions and high enantio- and stereoselectivities. The use of metagenomics has enabled new enzymes to be sourced with high sequence diversity. At UCL a metagenomics strategy has been developed for enzyme discovery, in which the library generated is annotated and searched for desired enzyme sequences. In this PhD, a metagenomic approach was used to retrieve 37 short chain reductase/dehydrogenases (SDRs) from an oral environment metagenome. Eight enzymes displayed activity towards cyclohexanone and their substrate selectivities were investigated. Four of the SDRs displayed activity to the Wieland-Miescher ketone (WMK), a motif found in several pharmaceutically relevant compounds. SDR-17 displayed high conversions and stereoselectivities and was co-expressed with the co-factor recycling enzyme glucose-6-phosphate dehydrogenase. This system was then successfully used to reduce (R)-WMK on a preparative scale reaction in 89% isolated yield and > 99% e.e. In further studies using reductases, the substrate specificities of two ketoreductases known as tropinone reductase I and II (TRI and TRII respectively) from the plant D. stramonium and MecgoR from E. coca were investigated. These studies expanded on reported substrate activities with these enzymes in the literature. A selection of symmetric and asymmetric tropinone analogues were synthesised, towards which MecgoR and TRI showed high activities, providing a strategy to access novel alcohols. Furthermore, sixteen ketoreductases were selected from a drain metagenome based on their sequence similarity of over 24% to MecgoR. They were annotated as aldo/keto reductases (ARKs) and five were successfully expressed in E. coli. Interestingly, the novel enzyme AKR-3 displayed activities toward aromatic ketones and aldehydes such as 2-indanone, phenylacetaldehyde and benzaldehyde. Transaminases (TAms) from the enzyme library toolbox at UCL were also tested with tropinone analogues and related cyclic compounds, several of which showed good activities.

24

Scaffidi, Adrian. "Synthetic endeavours in carbohydrates". University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0114.

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Abstract (sommario):

The overwhelming occurrence and structural diversity of carbohydrates in Nature indicate their importance in a range of fundamental life processes. Indeed, it is this diversity that has lead to the two equally diverse groups of carbohydrate-processing enzymes, namely the glycoside hydrolases and glycosyl transferases. Thus, understanding the role of both carbohydrates and their processing enzymes in biological systems has attracted significant attention. This thesis, firstly, describes endeavours towards the synthesis of an inositol ?- amino acid, along with a series of sugar α-substituted carboxylic acid esters, utilising an extension of the modified Corey-Link reaction. The emphasis of the thesis is then shifted towards the synthesis of a putative inhibitor of a family GH26 lichenase from Clostridium thermocellum (CtLic26A). The preparation of 2-deoxy-2-fluoro-β-laminarbiosyl fluoride 1 is described, along with elaboration into oligosaccharides utilising AbgE358G glycosynthase technology. Crystallographic investigations indicated that the transition state adopted by CtLic26A is in stark contrast to that utilised by the related family GH26 mannanase from Pseudomonas cellulose (Man26A). ... Following on from this work, expanding the role of the AbgE358G glycosynthase acceptor repertoire to accommodate inositol substrates was explored, furthering the synthetic utility of this enzyme. Thus, a number of inositol acceptors bearing an aryl anchor, for example 2, were prepared and shown to be surrogates for carbohydrate acceptors. ... The thesis then describes the synthesis of an acetamide derivative of 1-epivalienamine, namely 3, a putative inhibitor of β-N-acetylglucosaminidases. Both the synthesis of 3, along with kinetic data for four β-N-acetylglucosaminidases, is reported; as well, Western blot analysis indicated no inhibition of a recombinant OGTase. ... Related to the preparation of a putative inhibitor of β-N-acetylglucosaminidases was the synthesis of a conformationally rigid carbocycle derivative of PUGNAc 4, along with two other derivatives 5 and 6. These compounds were also tested against four β-N-acetylglucosaminidases and a recombinant OGTase. ... Finally, the synthesis of a mechanism-based inhibitor of family GH3 β-Nacetylglucosaminidases, namely 2-acetamido-2-deoxy-5-fluoro-β-D-glucopyranosyl fluoride 7, is described. The incorporation of an azido moiety allows for the utilisation of 8 as an effective probe of β-N-acetylglucosaminidases. ...

25

Chada, Sravanthi. "A new synthetic approach for preparation of efavirenz". Thesis, Nelson Mandela Metropolitan University, 2017. http://hdl.handle.net/10948/15512.

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Abstract (sommario):

Efavirenz, a drug that is still inaccessible to millions of people worldwide, is potent non nucleoside reverse transcriptase inhibitor (NNRTI), is one of the preferred agents used in combination therapy for first-line treatment of the human immunodeficiency virus (HIV). NNRTIs attach to and block an HIV enzyme called reverse transcriptase, by blocking reverse transcriptase; NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body. Efavirenz can't cure HIV/AIDS, but taken in combination with other HIV medicines (called an HIV regimen) every day helps people with HIV live longer healthier lives. Efavirenz also reduces the risk of HIV transmission and can be used by children who are suffering from HIV/AIDS. All the above therapeutic uses of efavirenz prompted us to identify the novel and hopefully cost efficient synthetic methodology for the preparation of efavirenz. In this thesis a new synthetic method for asymmetric synthesis of efavirenz is described. This route started from commercially available starting materials and it is first established in traditional batch chemistry and further the parameters transferred to a semi continuous flow protocol for optimization.

26

Oldfield, C. "The behaviour of enzymes in water-in-oil microemulsion systems". Thesis, University of Kent, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380705.

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27

Vousden, William Alexander. "Mutational analysis of the ACV synthetase gene of Aspergillus nidulans". Thesis, University of Sheffield, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366097.

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28

Sutherland, Andrew. "The enantioselective synthesis of amino acids for the investigation of protein structure". Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388029.

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29

Clough, Sarah. "Routes to the synthesis of oxygen containing heterocycles". Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301998.

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30

Feng, Jun. "A kinetic investigation of recombinant xenopus laevis amidating enzymes". Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/30084.

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31

Sampson, Peter B. "Synthesis of potential inhibitors targeting enzymes involved in methionine biochemistry". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0018/NQ53511.pdf.

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32

Johnson, Dean Vincent. "The synthesis of optically active chiral building blocks using enzymes". Thesis, University of Exeter, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317396.

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33

Watt, Alan. "Synthesis of novel benzotriazole substrates suitable for screening hydrolytic enzymes". Thesis, University of Edinburgh, 2002. http://hdl.handle.net/1842/11529.

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34

Lin, Jay. "Enzymes in thymidylate synthesis in Ureaplasma parvum as medical targets /". Uppsala : Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, 2009. http://epsilon.slu.se/11487069.pdf.

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35

Ndi, Cornelius Ndi. "Synthesis of Chemical Models of Hydrolase Enzymes for Intramolecular Catalysis". Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etd/1356.

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Abstract (sommario):

Most nuclease enzymes can hydrolyze phosphoester bonds (in DNA and RNA) by using metal ions cofactors that coordinate and activate water molecules in the enzymes' active sites. However, there are some hydrolase enzymes (including nucleases) that can function without the aid of metal ions. 2,6-Di(1H-imidazol-2-yl)phenol, a model compound for hydrolase enzyme, was synthesized by the reaction between ethylenediamine and dimethyl-3-carboxysalicylate, initially resulting in the formation of diimidazoline. The diimidazoline was subsequently aromatized to the diimidazole by dehydrogenation over palladium. The overall reaction yield was low; therefore, other dehydrogenation transformation reactions were tried but all failed to improve the yield. Converting this diimidazolphenol into diimidazolphenyl monophoshpate derivative was attempted but failed to give desired products. Synthesis of 2,2'-anthracene-1,8-diylbis-1H-imidazole, another model compound for hydrolase enzymes, was attempted using dimethyl-1,8-anthracenedicarboxylate, but synthesis was unsuccessful due to solubility problem.

36

Chen, Allen Kuan-Liang Biotechnology &amp Biomolecular Sciences Faculty of Science UNSW. "Enhanced biocatalyst production for (R)-phenylacetylcarbinol synthesis". Awarded by:University of New South Wales. School of Biotechnology and Biomolecular Sciences, 2006. http://handle.unsw.edu.au/1959.4/32825.

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Abstract (sommario):

The enzymatic production of R-phenylacetylcarbinol (R-PAC), with either whole cells or partially purified pyruvate decarboxylase (PDC) as the biocatalyst, requires high PDC activity and an inexpensive source of pyruvate for an economical feasible biotransformation process. Microbial pyruvate produced by a vitamin auxotrophic strain of Candida glabrata was selected as a potential substrate for biotransformation. With an optimal thiamine concentration of 60 ??g/l, a pyruvic acid concentration of 43 g/l and yield of 0.42 g/g glucose consumed were obtained. Using microbially-produced unpurified pyruvate resulted in similar PAC concentrations to those with commercial pure substrate confirming its potential for enzymatic PAC production. To obtain high activity yeast PDC, Candida utilis was cultivated in a controlled bioreactor. Optimal conditions for PDC production were identified as: fermentative cell growth at initial pH at 6.0 followed by pH downshift to 3.0. Average specific PDC carboligase activity of 392 ?? 20 U/g DCW was achieved representing a 2.7-fold increase when compared to a constant pH process. A mechanism was proposed in which the cells adapted to the pH decrease by increasing PDC activity to convert the accumulated internal pyruvic acid via acetaldehyde to ethanol thereby reducing intracellular acidification. The effect of pH shift on specific PDC activity of Saccharomyces cerevisiae achieved a comparable increase of specific PDC carboligase activity to 335 U/g DCW. The effect of pyruvic acid at pH 3.0 on induction of PDC activity was confirmed by cultivation at pH 3 with added pyruvic acid. Using microarray techniques, genome-wide transcriptional analyses of the effect of pH shift on S. cerevisiae revealed a transient increased expression of PDC1 after pH shift, which corresponded to the increase in specific PDC activity (although the latter was sustained for a longer period). The results showed significant gene responses to the pH shift with approximately 39 % of the yeast genome involved. The induced transcriptional responses to the pH shift were distinctive and showed only limited resemblance to gene responses reported for other environmental stress conditions, namely increased temperature, oxidative conditions, reduced pH (succinic acid), alkaline pH and increased osmolarity.

37

Rickaby, Kirstie. "Investigation of the chemo-enzymatic synthesis of cyclic peptides". Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=238613.

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Abstract (sommario):

Cyclic peptides constitute an attractive class of compounds for drug development, however the numerous problems associated with their synthesis have limited their applicability. The cyclisation step itself is particularly problematic, with solution phase cyclisations being required to be conducted under very high dilution to promote cyclisation over unwanted side reactions such as oligomerisation. In addition, epimerisation, leading to the loss of chiral integrity at the terminal residues is a major concern. Attention is now turning to biochemical cyclisation strategies, such as SICLOPPS and sortase mediated ligation, although these also come with their own inherent disadvantages, for example, in the case of sortase mediated ligation, there is significant “scarring” of the target due to the presence of a four amino acid long recognition sequence. Cyclisation using ribosomally synthesised post translationally modified enzymes is also gaining popularity. One such family of enzymes is the patellamides. PatGmac is capable of performing cyclisations on linear peptide substrates with minimal scarring compared to the aforementioned alternatives and, importantly, with no epimerisation and could constitute a greener and more facile route to cyclic peptides. The work herein details some of the investigations designed to define the range of synthetic utility and test the flexibility of the enzymes. This was done qualitatively, by designing a variety of linear peptide analogues of the natural product, homophymine A, featuring unique structural moieties and evaluating their compatibility with the enzyme. It was also done quantitatively, using an LCMS based semi-quantitative strategy, to assess differences between similar, but different, enzymes and to assess whether there were differences in how different substrates are processed by the same enzyme. In addition to this, a variety of these substrates were also assessed for their proclivity to cyclise under standard chemical conditions for comparison. Lastly, with the increasing appearance cyclic peptides and non-peptidic macrocycles in the libraries of compounds being considered for clinical trials, there is now a growing need for computational modelling of these structures. Herein, a 3D v structure for the natural product callipetin N is proposed for the first time, determined using a combination of computational and NMR techniques.

38

Simkovsky, Nadja Melitta. "Synthesis of some potential IKK inhibitors based around a pyrimidine scaffold". Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367619.

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39

Maddrell, Samuel James. "The application of organonitrile compounds to asymmetric synthesis". Thesis, University of Exeter, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294473.

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40

Aitken, D. J. "Approaches to selective synthesis using modified enzyme systems". Thesis, University of Strathclyde, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381516.

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41

Khan, Ahmed M. "Cyclic enzymatic solid phase synthesis of DNA oligonucleotides on an epoxide-activated resin [electronic resource] /". unrestricted, 2008. http://etd.gsu.edu/theses/available/etd-05082008-163131/.

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Abstract (sommario):

Thesis (M.S.)--Georgia State University, 2008.
Title from file title page. Markus W. Germann, committee chair; W. David Wilson, Kathryn B. Grant, committee members. Electronic text (51 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed July 14, 2008. Includes bibliographical references (p. 50-51).

42

Wharry, Thomas Scott. "The synthesis of novel phosphonate and phosphinate inhibitors of proteinase enzymes". Thesis, Queen's University Belfast, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263577.

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43

Wilks, Helen M. "Design and synthesis of new enzymes on the lactate dehydrogenase framework". Thesis, University of Bristol, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282796.

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44

Agyei-Owusu, Kwasi. "Synthesis and evaluation of novel inhibitors of thiamin diphosphate-dependent enzymes". Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608816.

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45

Jareño, Cerulla Júlia. "Synthesis of Mn/Fe heterodimers as model complexes for heterobimetallic enzymes". Thesis, Uppsala universitet, Institutionen för kemi - Ångström, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-225957.

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46

Mutthamsetty, Vinay. "Design and Synthesis of Amino Acid-based Inhibitors Against Key Enzymes". University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513014525316672.

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47

Storey, Benjamin 1973. "AQX : a novel gene in plant ubiquinone biosynthesis". Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80882.

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Abstract (sommario):

C. elegans worms with mutations in the gene CLK-1 develop slowly and have an extended lifespan. CLK-1 encodes a mitochondrial protein that is responsible for the hydroxylation of 5-demethoxyubiquinone (DMQ), the penultimate step of ubiquinone (Coenzyme-Q or UQ) biosynthesis. Structural homologues of CLK-1 are found in mammals, fruit flies, yeast and some types of bacteria. Interestingly, however, there is no structural homologue of CLK-1 in the Arabidopsis genome and no plant homologue can be found in other sequence databases. Yeast with the CLK-1 homologue COQ7 deleted fail to grow on non-fermentable carbon sources. To identify a plant functional homologue of COQ7/CLK-1, an Arabidopsis cDNA expression library was screened for complementation of a yeast coq7 deletion mutant. A clone was identified that rescued the coq7 respiratory deficiency. Although the sequence of the encoded protein has no structural similarity to proteins in the COQ7/CLK-1 family, it contains a monooxygenase/hydroxylase domain that has sequence similarity with the E. coli DMQ hydroxylase encoded by the UBIF gene. Like the structural homologues of COQ7/CLK-1 found in other eukaryotes, the gene (AQX for 'Alternate Quinone monooXygenase') contains a likely mitochondrial targeting presequence at its N-terminus. HPLC analysis of quinone extracts from rescued cog7 strains does not detect ubiquinone, but instead shows another peak that may be DMQ. It is likely that AQX does not hydroxylate yeast DMQ effectively enough to generate detectable levels of UQ. A unique pathway for UQ biosynthesis in plants is proposed that is defined by AQX and Arabidopsis genes identified on the basis of homology to known E. coli and yeast UQ biosynthesis genes.

48

Morgan, C. R. "Properties and synthesis of the ribulose-1,5-biphosphate carboxylase large subunit binding protein". Thesis, University of Warwick, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373050.

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49

Mitra, Adinpunya. "4-hydroxycinnamoyl-CoA hydratase/lyase from Pseudomonas fluorescens AN103 : characterisation and effects of expression in transformed root cultures of Datura stramonium". Thesis, University of East Anglia, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301994.

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50

Parikh, Bhargiv. "Design, Synthesis and Characterization of D-glucosamine Low Molecular Weight Gelators". ScholarWorks@UNO, 2010. http://scholarworks.uno.edu/td/1110.

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Low molecular weight gelators (LMWGs) have gained much attention over the last few decades, because of their ability to form supramolecular architectures as well as their many potential applications in biomedical research and as advanced materials. Most of the gelators were discovered through serendipity, and their structural requirements are somewhat ambiguous. This is due, in part, to the fact that the supramolecular gelation phenomenon is not yet fully understood, though many structural classes have been found to be excellent organogelators. Carbohydrates are abundant natural resources that are useful in preparing advanced materials. We have previously showed that monosaccharide derivatives can form effective low molecular weight gelators for both organic solvents and aqueous mixtures. In this research, we have studied the gelation capability of several glucosamine derivatives. Several series of 4,6-O-acetal protected glucosamine derivatives were synthesized and screened for their gelation properties in several solvents.