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1
Pérez-Breva, Luis. "DNA binding economies." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/42057.
Повний текст джерелаАнотація:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (p. 195-204).
This thesis develops a new scalable modeling framework at the interface of game theory and machine learning to recover economic structures from limited slices of data. Inference using economic models has broad applicability in machine learning. Economic structures underlie a surprisingly broad array of problems including signaling and molecular control in biology, drug development, neural structures, distributed control, recommender problems, social networking, as well as market dynamics. We demonstrate the framework with an application to genetic regulation. Genetic regulation determines how DNA is read and interpreted, is responsible for cell specialization, reaction to drugs, metabolism, etc. Improved understanding of regulation has potential to impact research on genetic diseases including cancer. Genetic regulation relies on coordinate binding of regulators along DNA. Understanding how binding arrangements are achieved and their effect on regulation is challenging since it is not always possible to study regulatory processes in isolation. Indeed, observing the action of regulators is an experimental and computational challenge. We need causal genome-wide models that can work with existing high-throughput observations. We abstract DNA binding as an economy and develop fast algorithms to predict average binding arrangements as competitive equilibria. The framework supports viewing regulation as a succession of regulatory states. We complete the framework with algorithms to infer causal structure from high-throughput observations. Learning here deviates from work in learning in games, it is closer to the economic theory of revealed preferences. Our algorithms predict the effect of experimental perturbations and can be used to refine experimental hypotheses. We show that the economic approach reproduces known behavior of a genetic switch (-phage), and that it can complete the map of coordinate binding in yeast.
by Luis Pérez-Breva.
Ph.D.
2
Umurtak, H. B. "Studies on DNA-binding peptides]." Thesis, University of Southampton, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235192.
Повний текст джерела
3
Pokhrel, Pujan. "Prediction of DNA-Binding Proteins and their Binding Sites." ScholarWorks@UNO, 2018. https://scholarworks.uno.edu/honors_theses/114.
Повний текст джерелаАнотація:
DNA-binding proteins play an important role in various essential biological processes such as DNA replication, recombination, repair, gene transcription, and expression. The identification of DNA-binding proteins and the residues involved in the contacts is important for understanding the DNA-binding mechanism in proteins. Moreover, it has been reported in the literature that the mutations of some DNA-binding residues on proteins are associated with some diseases. The identification of these proteins and their binding mechanism generally require experimental techniques, which makes large scale study extremely difficult. Thus, the prediction of DNA-binding proteins and their binding sites from sequences alone is one of the most challenging problems in the field of genome annotation. Since the start of the human genome project, many attempts have been made to solve the problem with different approaches, but the accuracy of these methods is still not suitable to do large scale annotation of proteins. Rather than relying solely on the existing machine learning techniques, I sought to combine those using novel “stacking technique” and used the problem-specific architectures to solve the problem with better accuracy than the existing methods. This thesis presents a possible solution to the DNA-binding proteins prediction problem which performs better than the state-of-the-art approaches.
4
Sando, Shinsuke. "RATIONAL DESIGN OF DNA-BINDING MOLECULES AND DNA PHOTOCLEAVERS." 京都大学 (Kyoto University), 2001. http://hdl.handle.net/2433/150700.
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5
Komori, Hirofumi. "Structural studies on DNA-binding proteins : DNA replication initiator and DNA photolyase." 京都大学 (Kyoto University), 2002. http://hdl.handle.net/2433/150005.
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6
Geary, Joella Suzanne. "DNA binding proteins of archaeal viruses." Thesis, Montana State University, 2008. http://etd.lib.montana.edu/etd/2008/geary/GearyJ1208.pdf.
Повний текст джерелаАнотація:
Archaea are single-celled organisms comprising the third domain of life. The Achaeal species Sulfolobus are infected by the Fuselloviridae virus family: SSV1, SSV2, SSV-RH, and SSV-K. The genomes of these viruses have been annotated and contain putative DNA-binding proteins. The purpose of this work is to identify DNA sequences bound by the SSV1 putative DNA-binding protein C43. C43 protein was cloned, expressed, purified, and assayed at various temperatures for interaction with three SSV1 DNA sequences. C43 binds the T5-promoter, T6-promoter, and C43-promoter sequentially and consistently. Additionally, C43 protein is functional at temperatures of 50°C and 65°C. Thus, C43 appears to be an important regulator of the Fuselloviridae SSV1 viral genome.
7
Bisset, Louise Clair. "Fluorescence of a DNA-binding protein." Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320129.
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8
Bullen, Gemma Anne. "Anthracene tagged biomolecules for DNA binding." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/6369/.
Повний текст джерелаАнотація:
Within this thesis, the use of anthracene to perform various applications within biomolecules is assessed. Anthracene displays two interesting photo properties which make it an appealing molecule for incorporation; fluorescence and photodimerisation. The former is utilised to develop a single nucleotide polymorphism detection assay which is shown to allow for determination of the base present in a complementary strand of DNA. In addition to this, the photodimerisation properties of anthracene are used within a protein for the first time. This is utilised to develop a photoswitched binding protein, allowing for control of DNA binding of the protein. Further to this, the photodimerisation properties are utilised within oligonucleotides to achieve structural control of a G-quadruplex as well as photo-triggered release of single stranded DNA.
9
Weinberg, Richard Lawrence. "The binding of p53 to DNA." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615988.
Повний текст джерела
10
Walavalkar, Ninad. "Structural basis of DNA binding complexes." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3162.
Повний текст джерелаАнотація:
The nucleosome remodeling and deacetylase (NuRD) complex is an abundant deacetylase complex, which couples histone deacetylation and chromatin remodeling ATPase activities, and has a broad cellular and tissue distribution. Although the working model of how this complex forms and functions is not well known, we have demonstrated that the coiled-coil interaction between two proteins (MBD2 and p66α) is critical for DNA methylation dependent gene silencing in vivo. Chapter one: ‘Unique features of the anti-parallel, heterodimeric coiled-coil interaction between methyl-cytosine binding domain 2 (MBD2) homologues and p66α dictate high affinity binding’ describes this unique coiled coil interaction. Coiled-coils were studied using a variety of biophysical techniques including analytical ultracentrifugation (AUC), isothermal titration calorimetry (ITC) and circular dichroism (CD). Results were compared across homologues and mutation studies were carried out to test our hypotheses. The studies reported in this chapter add to our understanding of coiled-coil interaction and thereby facilitate development of small peptide based drugs which target such interactions in nature.A number of proteins have been identified in humans that specifically bind to methylated CpG via a methyl binding domain (MBD). The human genome encodes at least five MBD proteins: MeCP2 and MBD1 through MBD4, which are homologous in their methyl binding domains but not many similarities are seen outside the MBD. Out of the five MBDs, MBD4 has a c-terminal glycosylase domain through which it recognizes mCpG.TpG mismatch and is important for base excision repair system. Chapter two: ‘Dynamic behavior of MBD4 in methylated DNA recognition’ focuses on MBD4 and its preference for DNA methylation mark. Techniques of surface plasmon resonance (SPR), nuclear magnetic resonance (NMR) spectroscopy are used to study binding affinity for variations of methylated DNA mark. Chemical exchange studies are used to demonstrate how MBD4 scans for methylation mark and these studies have added a new dimension to our understanding of how MBD proteins ‘read’ DNA methylation marks. Chapter three: ‘Solving the solution structure of MBD domain of MBD4 on methylated DNA by NMR’ describes a process of structure determination using NMR spectroscopy. The focus of this chapter is not on developing a new technique but rather on using current resources to solve a protein structure, which can be used to further understand our biological system. Here, I have discussed the workflow used to determine a final three-dimensional structure starting from sample preparation, data collection, data analysis to structure calculation.
11
Park, Frances E. "NF-kB DNA binding and transactivation /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2001. http://wwwlib.umi.com/cr/ucsd/fullcit?p3001261.
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Hlatshwayo, Nkosikhona Rejoyce. "Comparison of protein binding microarray derived and ChIP-seq derived transcription factor binding DNA motifs." Thesis, Rhodes University, 2015. http://hdl.handle.net/10962/d1017907.
Повний текст джерелаАнотація:
Transcription factors (TFs) are biologically important proteins that interact with transcription machinery and bind DNA regulatory sequences to regulate gene expression by modulating the synthesis of the messenger RNA. The regulatory sequences comprise of short conserved regions of a specific length called motifs . TFs have very diverse roles in different cells and play a very significant role in development. TFs have been associated with carcinogenesis in various tissue types, as well as developmental and hormone response disorders. They may be responsible for the regulation of oncogenes and can be oncogenic. Consequently, understanding TF binding and knowing the motifs to which they bind is worthy of attention and research focus. Various projects have made the study of TF binding their main focus; nevertheless, much about TF binding remains confounding. Chromatin immunoprecipitation in conjunction with deep sequencing (ChIP-seq) techniques are a popular method used to investigate DNA-TF interactions in vivo. This procedure is followed by motif discovery and motif enrichment analysis using relevant tools. Protein Binding Microarrays (PBMs) are an in vitro method for investigating DNA-TF interactions. We use a motif enrichment analysis tools (CentriMo and AME) and an empirical quality assessment tool (Area under the ROC curve) to investigate which method yields motifs that are a true representation of in vivo binding. Motif enrichment analysis: On average, ChIP-seq derived motifs from the JASPAR Core database outperformed PBM derived ones from the UniPROBE mouse database. However, the performance of motifs derived using these two methods is not much different from each other when using CentriMo and AME. The E-values from Motif enrichment analysis were not too different from each other or 0. CentriMo showed that in 35 cases JASPAR Core ChIP-seq derived motifs outperformed UniPROBE mouse PBM derived motifs, while it was only in 11 cases that PBM derived motifs outperformed ChIP-seq derived motifs. AME showed that in 18 cases JASPAR Core ChIP-seq derived motifs did better, while only it was only in 3 cases that UniPROBE motifs outperformed ChIP-seq derived motifs. We could not distinguish the performance in 25 cases. Empirical quality assessment: Area under the ROC curve values computations followed by a two-sided t-test showed that there is no significant difference in the average performances of the motifs from the two databases (with 95% confidence, mean of differences=0.0088125 p-value= 0.4874, DF=47) .
13
Goddard, C. "DNA and chromatin binding by the methyl-CpG-binding protein, MeCP2." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599452.
Повний текст джерелаАнотація:
In eukaryotes, methylation at CpG dinucleotides causes transcriptional repression. MeCP2 is a good candidate for a transducer of this methylation signal as it is capable of binding to methylated DNA and can repress transcription in vitro. This thesis describes experiments to further investigate the DNA and chromatin binding properties of MeCP2. Chapter 2 describes the subcloning, overexpression and purification of recombinant rat MeCP2 and also the purification of native MeCP2 from rat brain. The similarity in purification protocols indicates that the recombinant protein is a good model for the native protein. Chapter 3 describes in vitro assays for DNA and chromatin binding. The DNA binding assays confirm that MeCP2 binds to both methylated and unmethylated DNA but has a preference for methylated DNA. The chromatin binding assays show that MeCP2 binds chromatin of all lengths in vitro and most evidence indicates that it is capable of displacing histone H1. Crosslinking experiments showed that MeCP2 crosslinks to core histones and maybe also to itself. The electrophoretic mobility shift assay and also the arrangement of endogenous MeCP2 in native chromatin indicate that MeCP2 may exhibit co-operativity. The crosslinking data suggested that co-operativity may be mediated by protein-protein interactions but this was shown not to be the case by gel filtration. Another possibility was that MeCP2 arrays could be protected by higher order folding. Analytical ultracentrifugation and electron microscopic analysis show that MeCP2 does not induce higher order folding itself. It may be that other factors cause folding of inactive chromatin and protect MeCP2 arrays. The in vitro data indicates that MeCP2 acts non-specifically. In the work described in Chapter 4, a chromatin immunoprecipitation (ChIP) assay was used to investigate whether MeCP2 displays specificity in vivo. It was found that MeCP2 binds NSE, Mash2, H19 and HPRT, but not GAPDH in both female rat brain and female rat liver nuclei, and to ADH in female rat brain but not female rat liver nuclei.
14
Sheldon, Deuser Shelby Diane. "Two-site DNA Minor Groove Binding Compounds." Digital Archive @ GSU, 2012. http://digitalarchive.gsu.edu/chemistry_theses/51.
Повний текст джерелаАнотація:
DNA minor groove binding compounds have had limited therapeutic uses, in part due to problems with sequence specificity. A two-site model has been developed to enhance specificity, in which compounds bind to two short AT sites separated by one or two GC base pairs. Using thermal melting, heterocyclic dications with this capability were tested with various oligonucleotides for binding affinity and specificity. Compounds of interest were further probed using circular dichroism, mass spectrometry, biosensor-SPR, and molecular modeling. Several compounds were found to “jump” a GC base pair, binding to AT sites in the minor groove of DNA with a two-site recognition mode. One compound was also found to recognize a single intervening GC base pair. Compounds with terminal, non-polar amidine extensions were found to have increased DNA binding compared to analogs with terminal amidines. This unique, two-site DNA recognition mode offers novel design principles to recognize entirely new DNA motifs.
15
Moon, Nam Sung 1972. "Modes and regulations of CDPCux DNA binding." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38244.
Повний текст джерелаАнотація:
The CDP/Cux transcription factor contains four DNA binding domains: three Cut repeats (CR1, CR2 and CR3) and the Cut homeodomain (HD). The CCAAT-displacement protein (CDP) was first identified as it represses transcription of certain promoters by competing for the occupancy of the CCAAT sequence. CDP was then found to be the ortholog of the Drosophila Cut protein (Cux: Cu t homeobox&barbelow;). The goal of my project was to define the modes of interactions of CDP/Cux with DNA. I demonstrated that high affinity DNA binding requires the cooperation between at least two of the CDP/Cux DNA binding domains. Among all combinations of domains, Cut repeats 1 and 2 (CR1CR2) and Cut repeat 3 and the Cut homeodomain (CR3HD) exhibited the highest DNA binding affinities, but with different kinetics and specificities. Whereas CR1CR2 bound with fast kinetics to dimers of CART or CGAT, CR3HD bound to ATCGAT with slow kinetics. CR1CR2 was shown to be responsible for the CCAAT displacement activity of CDP/Cux. Surprisingly, the full-length CDP/Cux protein, p200, exhibited DNA binding properties similar to that of CR1CR2, indicating that CR3HD is inactive in this context. However, an amino terminally truncated 110 KDa CDP/Cux isoform capable of stable interaction with DNA was identified in cellular extracts. The p110 isoform was shown to be generated by proteolytic cleavage of p200 at the G1/S transition. The p200 and p110 isoforms displayed different transcriptional activities in reporter assays, as only p110 was able to activate transcription from the DNA polymerase a gene promoter. Interestingly, expression of p110 was found to be increased in human uterine leiomyomas as compared to the adjacent normal myometrium, raising the possibility that proteolytic processing of CDP/Cux is activated in cancer cells. Finally, cyclin D/CDK4 was shown to interact with CDP/Cux, phosphorylate it on several serine residues and inhibit proteolytic processing as well as DNA binding by CR3HD. Repla
16
Choo, Yen. "Design of site-specific DNA-binding proteins." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363127.
Повний текст джерела
17
Broome, Mark John. "Interaction of DNA with groove binding ligands." Thesis, University of Warwick, 2008. http://wrap.warwick.ac.uk/1933/.
Повний текст джерелаАнотація:
Synthetic molecules that target the major groove in a sequence-selective way are a major goal in molecular medicine. Recently a major step has been taken toward achieving this goal: a novel cylinder has been developed that binds strongly into the major groove of DNA. Experimental techniques have provided some information regarding the binding strength and preferred binding sites of the cylinder on DNA. From all the experimental data it is clear that the parent cylinder binds in the major groove and is able to induce dramatic conformational changes in the DNA; these are unprecedented effects with synthetic DNA binders. However, gaining molecular level information in such a macromolecular system is challenging. Molecular dynamics (MD) simulations can provide information at the molecular level that is complementary to experiment and therefore are an ideal way to get a better understanding of this system. In this work we present the results of various MD simulations designed to probe the DNA-cylinder system. We have studied the effect of using CHARMM22 and CHARMM27 as the force-field for the simulations. Results showed that uncomplexed DNA simulated with CHARMM22 was less stable in the B-form than the comparable strand of DNA simulated with CHARMM27. Investigations into the effects of the cylinders charge and shape are also reported. Multi-nanosecond simulations were performed using two related synthetic cylinders, one with two Fe(II) metal centers and the other with two Cu(I) centers, and DNA. Finally the role of DNA within the system was investigated by performing a series of simulations of the cylinders with d(ATATATATATAT)2, d(CGCGCGCGCGCG)2 and d(CGCGCATATACG). Simulations with these DNA strands has only produced one system (CCu2+ with d(ATATATATATAT)) where the cylinder causes a conformational change in the DNA.
18
Simanis, V. "T antigen binding sequences in cellular DNA." Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37854.
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19
Leczkowska, Anna. "Non-covalent DNA-binding ruthenium anticancer drugs." Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/1695/.
Повний текст джерелаАнотація:
The research work described in this thesis concerns metal-based anticancer drugs with an emphasis on non-covalent DNA-binding supramolecular assemblies. The project involves the preparation of a series of mono- and bi-metallic ruthenium complexes with a primary focus on fluorescent dinuclear triple-stranded helicates with different structural topographies. Emphasis is then directed towards an investigation of the DNA binding characteristics of these molecules and an evaluation of their anticancer properties in human cancer cell lines. Attention is brought to the significance that the cylinder-building moieties and their structural characteristics have to these features. The studies also include an examination of the effects of chirality of the investigated supramolecular systems and the impact they have on molecular recognition. This is addressed via studies of the interaction of optical isomers of ruthenium triple-stranded helicates with DNA as a biomolecular target system and with Δ-TRISPHAT as a representative small chiral molecule.
20
Rodríguez, Armando Chapin. "Structure-function studies of DNA-binding motors." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619565.
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21
Nickols, Nicholas George Mayo Stephen L. Dervan Peter B. "Endogenous gene regulation by DNA binding polyamides /." Diss., Pasadena, Calif. : California Institute of Technology, 2008. http://resolver.caltech.edu/CaltechETD:etd-06212007-155330.
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Gapian, Bianké Jean-Paul. "DNA mimics containing artificial metal-binding sites /." [S.l.] : [s.n.], 2006. http://www.zb.unibe.ch/download/eldiss/06bianke_g.pdf.
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23
Schilter, David. "Synthesis and DNA-binding of Metallocyclic Architectures." Thesis, The University of Sydney, 2009. http://hdl.handle.net/2123/5317.
Повний текст джерелаАнотація:
A new family of cationic N-heterocyclic ligand derivatives was prepared and characterised. Among these compounds are halide salts of the dications [Y(spacer)Y]2+, each of which comprise two N heterocyclic donor groups (Y = 4,4′-bipy, pyz, apyz, apym) linked by a conformationally flexible spacer such as (CH2)n, α,α′-xylylene, 2,6-lutidylene or thiabicyclo[3.3.1]nonane-2,6 diyl. The diquaternary halide salts were converted to NO3- and PF6- salts, and interaction of these bridging ligands with labile palladium(II) and platinum(II) precursors afforded several multinuclear complexes. Bis(4,4′-bipyridinium) dications were incorporated into the dinuclear macrocycles [M2(2,2′ bipy)2{4,4′ bipy(CH2)n4,4′-bipy}2]8+ (M = Pd, Pt; n = 4, 6), cis [Pd2Cl4{4,4′ bipy(CH2)34,4′-bipy}2]4+, [Pt2(dppp)2{4,4′-bipy(1,2-xylylene)4,4′-bipy}2]8+ and cis-[Pt2Cl4{4,4′-bipy(1,2-xylylene)4,4′-bipy}2]4+. While bis(pyrazinium) analogues were unreactive towards the palladium(II) and platinum(II) precursors, the doubly deprotonated bis(3 aminopyrazinium) and bis(2 aminopyrimidinium) derivatives served as charge-neutral quadruply-bridging ligands in the complexes [Pt4(2,2′ bipy)4{apyz(CH2)6apyz–2H}2]8+ and [Pt4(2,2′ bipy)4{apym(CH2)5apym–2H}2]8+, both of which feature Pt(II). Pt(II) interactions. Larger species formed when the diamine O,O′-bis(2-aminoethyl)octadeca(ethylene glycol) (PEGda) was treated with cis dinitratopalladium(II) and platinum(II) precursors. The resulting complexes [M(N,N)(PEGda)]2+ (M = Pd, Pt; N,N = 2,2′-bipy, en, tmeda) possessed great size (62 membered chelate rings) and aqueous solubility. DNA-binding studies were conducted with selected complexes in order to investigate the types of interactions these species might participate in. Equimolar mixtures containing either the 16mer duplex DNA D2 or the single strand D2a and palladium(II)/platinum(II) complexes were prepared and analysed by negative-ion ESI MS. Studies of D2/Pd(II) mixtures suggested extensive fragmentation was occuring, and the use of [Pd(tmeda)(PEGda)]2+ and [Pd2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+ resulted in D2 adducts of [Pd(tmeda)]2+ and [4,4′-bipy(CH2)44,4′-bipy]2+, respectively. Decomposition also occurred when D2a was used, although 1 : 1 adducts were observed with [Pd(tmeda)(PEGda)]2+, [Pd(2,2′ bipy)(PEGda)]2+ and [Pd2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+. The low intensities of these adducts indicated that they are unstable towards ESI MS. Analogous ESI-MS experiments using platinum(II) derivatives were performed and, in contrast to those with palladium(II), indicated that the complexes remained largely intact. ESI-MS analysis of D2/Pt(II) mixtures allowed for the detection of 1 : 1 D2 adducts of [Pt(en)(PEGda)]2+, [Pt(tmeda)(PEGda)]2+ and [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+. Intensities of the adduct ions suggested the greater charge and aryl surface area allow the dinuclear species to bind D2 most strongly. Both [Pt(2,2′-bipy)(Mebipy)2]4+ and [Pt(2,2′ bipy)(NH3)2]2+ gave rise to 1 : 2 adducts of D2, although the latter was found to be a weaker binder, perhaps owing to its lower charge. Data obtained using 1 : 5 (D2 : complex) mixtures were consistent with the results above and suggested that D2 can bind more molecules of daunomycin than any of the platinum(II) species. Analyses of D2a/Pt(II) mixtures gave results similar to those obtained with D2, although fragmentation was more pronounced, indicating that the nucleobases in D2a play more significant roles in mediating decomposition than those in D2, in which they are paired in a complementary manner. Investigations into the effects of selected platinum(II) complexes on the thermal denaturation of calf-thymus DNA (CT-DNA) in solution were conducted. Both [Pt2(2,2′ bipy)2{4,4′-bipy(CH2)64,4′-bipy}2]8+ and [Pt(2,2′-bipy)(Mebipy)2]4+ greatly stabilised CT-DNA, most likely by intercalation. In contrast, [Pt(tmeda)(PEGda)]2+ and [Pt(en)(PEGda)]2+ (as well as PEGda) caused negligible changes in melting temperature (∆Tm), suggesting that these interact weakly with CT-DNA. Data for [Pt(2,2′ bipy)(PEGda)]2+ and [Pt(2,2′-bipy)(NH3)2]2+ indicated that these species perhaps intercalate CT-DNA, with similar ∆Tm values for both complexes implying that PEGda does not play a major role in binding. While findings from ESI-MS experiments were similar to those from the thermal denaturation experiments, discrepancies between results from the two methods could be found. In particular, fragmentation of cyclic species during ESI-MS caused the binding strength of the species to be underestimated when this method was employed.
24
Schilter, David. "Synthesis and DNA-binding of Metallocyclic Architectures." University of Sydney, 2009. http://hdl.handle.net/2123/5317.
Повний текст джерелаАнотація:
PhDA new family of cationic N-heterocyclic ligand derivatives was prepared and characterised. Among these compounds are halide salts of the dications [Y(spacer)Y]2+, each of which comprise two N heterocyclic donor groups (Y = 4,4′-bipy, pyz, apyz, apym) linked by a conformationally flexible spacer such as (CH2)n, α,α′-xylylene, 2,6-lutidylene or thiabicyclo[3.3.1]nonane-2,6 diyl. The diquaternary halide salts were converted to NO3- and PF6- salts, and interaction of these bridging ligands with labile palladium(II) and platinum(II) precursors afforded several multinuclear complexes. Bis(4,4′-bipyridinium) dications were incorporated into the dinuclear macrocycles [M2(2,2′ bipy)2{4,4′ bipy(CH2)n4,4′-bipy}2]8+ (M = Pd, Pt; n = 4, 6), cis [Pd2Cl4{4,4′ bipy(CH2)34,4′-bipy}2]4+, [Pt2(dppp)2{4,4′-bipy(1,2-xylylene)4,4′-bipy}2]8+ and cis-[Pt2Cl4{4,4′-bipy(1,2-xylylene)4,4′-bipy}2]4+. While bis(pyrazinium) analogues were unreactive towards the palladium(II) and platinum(II) precursors, the doubly deprotonated bis(3 aminopyrazinium) and bis(2 aminopyrimidinium) derivatives served as charge-neutral quadruply-bridging ligands in the complexes [Pt4(2,2′ bipy)4{apyz(CH2)6apyz–2H}2]8+ and [Pt4(2,2′ bipy)4{apym(CH2)5apym–2H}2]8+, both of which feature Pt(II). Pt(II) interactions. Larger species formed when the diamine O,O′-bis(2-aminoethyl)octadeca(ethylene glycol) (PEGda) was treated with cis dinitratopalladium(II) and platinum(II) precursors. The resulting complexes [M(N,N)(PEGda)]2+ (M = Pd, Pt; N,N = 2,2′-bipy, en, tmeda) possessed great size (62 membered chelate rings) and aqueous solubility. DNA-binding studies were conducted with selected complexes in order to investigate the types of interactions these species might participate in. Equimolar mixtures containing either the 16mer duplex DNA D2 or the single strand D2a and palladium(II)/platinum(II) complexes were prepared and analysed by negative-ion ESI MS. Studies of D2/Pd(II) mixtures suggested extensive fragmentation was occuring, and the use of [Pd(tmeda)(PEGda)]2+ and [Pd2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+ resulted in D2 adducts of [Pd(tmeda)]2+ and [4,4′-bipy(CH2)44,4′-bipy]2+, respectively. Decomposition also occurred when D2a was used, although 1 : 1 adducts were observed with [Pd(tmeda)(PEGda)]2+, [Pd(2,2′ bipy)(PEGda)]2+ and [Pd2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+. The low intensities of these adducts indicated that they are unstable towards ESI MS. Analogous ESI-MS experiments using platinum(II) derivatives were performed and, in contrast to those with palladium(II), indicated that the complexes remained largely intact. ESI-MS analysis of D2/Pt(II) mixtures allowed for the detection of 1 : 1 D2 adducts of [Pt(en)(PEGda)]2+, [Pt(tmeda)(PEGda)]2+ and [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+. Intensities of the adduct ions suggested the greater charge and aryl surface area allow the dinuclear species to bind D2 most strongly. Both [Pt(2,2′-bipy)(Mebipy)2]4+ and [Pt(2,2′ bipy)(NH3)2]2+ gave rise to 1 : 2 adducts of D2, although the latter was found to be a weaker binder, perhaps owing to its lower charge. Data obtained using 1 : 5 (D2 : complex) mixtures were consistent with the results above and suggested that D2 can bind more molecules of daunomycin than any of the platinum(II) species. Analyses of D2a/Pt(II) mixtures gave results similar to those obtained with D2, although fragmentation was more pronounced, indicating that the nucleobases in D2a play more significant roles in mediating decomposition than those in D2, in which they are paired in a complementary manner. Investigations into the effects of selected platinum(II) complexes on the thermal denaturation of calf-thymus DNA (CT-DNA) in solution were conducted. Both [Pt2(2,2′ bipy)2{4,4′-bipy(CH2)64,4′-bipy}2]8+ and [Pt(2,2′-bipy)(Mebipy)2]4+ greatly stabilised CT-DNA, most likely by intercalation. In contrast, [Pt(tmeda)(PEGda)]2+ and [Pt(en)(PEGda)]2+ (as well as PEGda) caused negligible changes in melting temperature (∆Tm), suggesting that these interact weakly with CT-DNA. Data for [Pt(2,2′ bipy)(PEGda)]2+ and [Pt(2,2′-bipy)(NH3)2]2+ indicated that these species perhaps intercalate CT-DNA, with similar ∆Tm values for both complexes implying that PEGda does not play a major role in binding. While findings from ESI-MS experiments were similar to those from the thermal denaturation experiments, discrepancies between results from the two methods could be found. In particular, fragmentation of cyclic species during ESI-MS caused the binding strength of the species to be underestimated when this method was employed.
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Preston, Nicola Susan. "Structure and DNA binding of HMG boxes." Thesis, University of Portsmouth, 1996. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310386.
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Cruickshank, Jennifer. "The DNA binding mechanism of the Epstein-Barr origin binding protein, EBNA1." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0006/MQ46091.pdf.
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Phillips, Christine M. (Christine Marie). "Relating metal binding to DNA binding in the nickel regulatory protein NikR." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/57569.
Повний текст джерелаАнотація:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Vita. Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
The concentration of transition metals within the cell must be tightly regulated. If the concentration of a given transition metal is too low the cell may not be able to perform life-sustaining processes, while high levels of metals are poisonous to the cell and can cause cell death. In Escherichia coli, NikR regulates nickel uptake by blocking transcription of the genes encoding the nickel uptake transporter, NikABCDE. NikR is a homotetrameric transcription factor with a central metal binding domain (MBD) that includes the tetrameric interface and two flanking dimeric ribbon-helix-helix (RHH) DNA-binding domains. Early work revealed that NikR can bind a variety of transition metal ions and has two binding affinities for the nik operon: nM when stoichiometric Ni2+ binds NikR and pM when excess Ni2+ binds. The enhanced DNA affinity suggests the presence of low affinity nickel binding sites on the protein. Recently, it has been shown that NikR also requires K+ to bind DNA, suggesting yet another type of metal binding site on the protein. To understand NikR's ability to bind multiple transition metal ions and how Ni2+ specifically induces NikR-DNA binding, we solved the crystal structures of the apo- MBD and BMD bound to Zn2+ and Cu2+. Comparing these structures to the previously published Ni2+-MBD structure, we noted that when the proper metal binds to NikR it utilizes H76 of alpha helix 3 as a ligand. This, in turn, orders helix !3, and we propose this conformational stabilization is a key step in the NikR-DNA binding mechanism. Electrostatic free energy calculations and thermodynamic integration were used to study which metal prefers to bind at a site between the MBD and RHH domains that is formed when NikR is bound to DNA. Our studies illustrate that NikR-DNA binding was most favorable when this site contains a monovalent cation the size of K+. These studies support a physiological role of K+ in NikR-DNA binding. Structures from crystals of NikR and NikR-bound to DNA soaked with excess nickel ions indicate six types of potential low-affinity nickel binding sites on the protein surface. Binding of excess nickel ions to these sites does not induce any significant conformational change, suggesting that these sites have an electrostatic effect increasing ! 4 NikR's affinity for DNA. Using a combination of X-ray crystallography and molecular simulations we have identified and explored the metal binding sites on E. coli NikR and how they influence NikR:DNA binding.
by Christine M Phillips.
Ph.D.
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Roberts, Jennifer Nicole. "Investigating the DNA binding properties of the Telomere End-Binding Protein Cdc13." Connect to online resource, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3337145.
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Luo, Dan. "Novel cross-linking technologies to assess protein-DNA binding and DNA-DNA complexes for gene delivery and expression /." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487946776022443.
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Watts, Richard A. "Relationship between a fetal DNA-binding antibody and the DNA-binding antibodies produced by patients with systemic lupus erythematosus." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.291603.
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Andrade, Helena. "DNA Oligomers - From Protein Binding to Probabilistic Modelling." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-218709.
Повний текст джерелаАнотація:
This dissertation focuses on rationalised DNA design as a tool for the discovery and development of new therapeutic entities, as well as understanding the biological function of DNA beyond the storage of genetic information. The study is comprised of two main areas of study: (i) the use of DNA as a coding unit to illustrate the relationship between code-diversity and dynamics of self-assembly; and (ii) the use of DNA as an active unit that interacts and regulates a target protein.
In the study of DNA as a coding unit in code-diversity and dynamics of self-assembly, we developed the DNA-Based Diversity Modelling and Analysis (DDMA) method. Using Polymerase Chain Reaction (PCR) and Real Time Polymerase Chain Reaction (RT-PCR), we studied the diversity and evolution of synthetic oligonucleotide populations. The manipulation of critical conditions, with monitoring and interpretation of their effects, lead to understanding how PCR amplification unfolding could reshape a population. This new take on an old technology has great value for the study of: (a) code-diversity, convenient in a DNA-based selection method, so semi-quantitation can evaluate a selection development and the population\'s behaviour can indicate the quality; (b) self-assembly dynamics, for the simulation of a real evolution, emulating a society where selective pressures direct the population's adaptation; and (c) development of high-entropy DNA structures, in order to understand how similar unspecific DNA structures are formed in certain pathologies, such as in auto-immune diseases.
To explore DNA as an active unit in Tumour Necrosis Factor α (TNF-α) interaction and activity modulation, we investigate DNA's influence on its spatial conformation by physical environment regulation. Active TNF-α is a trimer and the protein-protein interactions between its monomers are a promising target for drug development. It has been hypothesised that TNF-α forms a very intricate network after its activation between its subunits and receptors, but the mechanism is still not completely clear. During our research, we estimate the non-specific DNA binding to TNF-α in the low micro-molar range. Cell toxicity assays confirm this interaction, where DNA consistently enhances TNF-α's cytotoxic effect. Further binding and structural studies lead to the same conclusion that DNA binds and interferes with TNF-α structure. From this protein-DNA interaction study, a new set of tools to regulate TNF-α's biological activity can be developed and its own biology can be unveiled.
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Nilsson, Mikael. "Protein-DNA recognition : in vitro evolution and characterization of DNA-binding proteins /." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4269.
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Burton, Sara Katherine. "DNA-binding proteins associated with DNA polymerase alpha in pea (Pisum sativum)." Thesis, University of Exeter, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357961.
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Slayton, Mark D. "Protein-DNA Interactions of pUL34, an Essential Human Cytomegalovirus DNA-Binding Protein." Ohio University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1533638730703166.
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James, Daniel Peter. "Computational methods for the measurement of protein-DNA interactions." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/277257.
Повний текст джерелаАнотація:
It is of interest to know where in the genome DNA binding proteins act in order to effect their gene regulatory function. For many sequence specific DNA binding proteins we plan to predict the location of their action by having a model of their affinity to short DNA sequences. Existing and new models of protein sequence specificty are investigated and their ability to predict genomic locations is evaluated. Public data from a micro-fluidic experiment is used to fit a matrix model of binding specificity for a single transcription factor. Physical association and disassociation constants from the experiment enable a biophysical interpretation of the data to be made in this case. The matrix model is shown to provide a better fit to the experimental data than a model initially published with the data. Public data from 172 protein binding micro-array experiments is used to fit a new type of model to 82 unique proteins. Each experiment provides measurements of the binding specificity of an individual protein to approximately 40000 DNA probes. Statistical, `DNA word', models are assessed for their ability to predict held back data and perform very well in many cases. Where available, ChIP-seq data from the ENCODE project is used to assess the ability of a selection of the DNA word models to predict ChIP-seq peaks and how they compare to matrix models in doing so. This $\textit{in vitro}$ data is the closest proxy to the true sites of the proteins' regulatory action that we have.
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Rehmani, Imran J. "Studying the DNA Binding and Conformation of Metal-Binding Site Mutations in Pirin." Digital Archive @ GSU, 2012. http://digitalarchive.gsu.edu/chemistry_theses/53.
Повний текст джерелаАнотація:
The transcription factor NF-κB interacts with many other co-regulator proteins that modulate its binding and transcriptional activity. One of these co-regulators, Pirin, is an iron-dependent metalloprotein that has been shown to enhance the DNA binding of NF-κB homodimers. Here, we characterize the interactions between Pirin and its known NF-κB binding partners and examined the role of Bcl-3, a protein that is required for Pirin’s interaction with p50. In addition, we use site-directed mutagenesis to alter conserved residues within Pirin’s metal binding environment and observed how it affected the DNA binding and conformation of the Pirin-NF-κB complex. These studies show that, while a similar enhancing effect on DNA binding is observed, the interactions of Pirin with different NF-κB members are distinct from each other and could possibly have different physiological purposes.
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Goytisolo, Fermin Alejandro. "DNA and chromatin binding sites on histone H5." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262871.
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Daly, Colette Lynn. "Binding studies using membrane electrodes." Thesis, University of Salford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252942.
Повний текст джерелаАнотація:
The research embodied within this thesis has contributed to the development and application of a novel electrode technique. The electrodes fabricated herein consist of a thin PVC/Poly (vinylchloride) membrane which is made sensitive to a particular organic cation, for example Acridine Orange. The only requirements necessary to make an electrode were that the substance to be incorporated into the membrane be cationic, water soluble and surface active. These membrane electrodes gave an emf directly proportional to the log of the ( concentration of organic cations present in solution.
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Fouquier, d'Herouel Aymeric. "Statistical models of TF/DNA interaction." Licentiate thesis, Stockholm : Numerisk analys och datalogi, Numerical Analysis and Computer Science, Kungliga Tekniska högskolan, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4633.
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Sunstrom, Noëlle-Ann. "Specific DNA binding by polyomavirus large T antigen." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=70257.
Повний текст джерелаАнотація:
To define the DNA binding domain of polyomavirus large T antigen, systematic deletion mutagenesis was carried out on large T antigen. A set of plasmids coding for unidirectional carboxy- or amino-terminal deletion mutations in large T antigen were constructed. Deleted proteins were expressed by plasmid transfection of Cos-1 cells. Analysis of origin-specific DNA binding by mutant proteins revealed that the C-terminal boundary of the DNA-binding domain is at or near Glu 398. Fusion proteins of large T antigen lacking the first 200 N-terminal amino acids bound specifically to polyomavirus origin DNA; however, deletions beyond this site resulted in unstable proteins which could not be tested for DNA binding. Testing of point mutants and internal deletions by others suggest that the N-terminal boundary of the DNA-binding domain lies between amino acids 282 and 286. Taken together, these results locate the DNA-binding domain of polyomavirus large T antigen to the 116- amino acid region between residues 282 and 398.Polyomavirus large T antigen binds to four discrete regions within the regulatory region of the viral genome. The relative arrangement of these binding sites may be important for the distinct regulatory functions performed by the protein. Each of the four large T antigen binding sites was separately cloned into a test plasmid by the use of oligonucleotide-directed mutagenesis. The binding affinity of large T antigen was analyzed for each individual site and for combinations of sites. The results of this analysis showed that there exists an hierarchy of binding strength among individual and combinations of large T antigen binding sites as measured by DNA immunoprecipitation. In addition, the DNA binding of large T antigen involves cooperative interaction of protein molecules between adjacent binding sites, and the integrity of the amino terminus is required for cooperativity.
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Jacobs, Grant H. "Computer analysis of motifs in DNA binding proteins." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259565.
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42
Gill, Martin. "DNA-binding ruthenium complexes : cellular imaging and cytotoxicity." Thesis, University of Sheffield, 2010. http://etheses.whiterose.ac.uk/1161/.
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Menderin, Nathan. "Studies on the Human Sp1 DNA-Binding Domain." Thesis, University of Exeter, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507135.
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Fairweather, Victoria S. S. "Biophysical characterisation of DNA-binding proteins and oxidoreductases." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508074.
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Hill, G. R. "NMR studies of DNA and RNA binding proteins." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604060.
Повний текст джерелаАнотація:
HMG-D is a 112-residue, non-histone chromosomal protein from Drosophila melanogaster and is a member of the class of non-sequence specific HMGB proteins. The present project was based on the observation that other HMGB complexes that had been solved by NMR had a phenylalanine residue at a key interfacial location (corresponding to position 12 in HMG-D), whereas those like HMG-D that gave few intermolecular NOE cross peaks generally had a tyrosine at this location. This tyrosine was known to be involved in hydrogen-bonding to the DNA in a related complex that had been solved crystallographically. The Y12F mutant of full-length HMG-D was expressed and purified in isotope-labelled form suitable for NMR spectroscopy, and a set of multidimensional triple resonance experiments used to derive assignments for the backbond resonances of the protein both free and in complex with the dA2 bulge DNA. Sidechain assignments for the protein were obtained by a combination of “CCH”-transfer-based experiments and NOE spectra, while nearly complete assignments for the DNA in the complex were obtained from a combination of homonuclear 2D NOESY and TOCSY experiments together with filtered NOESY experiments where just cross peaks between protons both of which were not coupled to heteronuclei were selected. Filtered NOESY-based experiments were used to observe intermolecular NOE cross peaks in isolation, and, in contrast to the case of the wild-type complex, these experiments yielded around 50 intermolecular interactions. Together with an extensive set of assigned intramolecular NOE constraints, these formed the basis for a calculation of the structure of the complex starting from random conformations of both protein and DNA chains, which resulted in an NMR structure for the complex that had good precision over the structured region (residues 3-70 of the protein and stem 1 of the DNA).
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Maynard, Allister J. "NMR studies of protein folding and DNA binding." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313244.
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Povey, Jane. "Structural studies of the DNA-binding protein GAL4." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385462.
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Scarpantonio, Luca. "Studies of DNA binding of lanthanide platinum complexes." Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/2860/.
Повний текст джерелаАнотація:
Using supramolecular principles, we have been designing luminescent lanthanide complexes with a defined hairpin bis-interlacator in order to obtain luminescent probes able to recognise DNA. The complexes are comprised of Platinum(II) terpyridine, which acts as a DNA recognition site and is brought together with a "remote" luminescent lanthanide unit. All the synthetic approaches were based on the accessibility of the lanthanide-platinum complexes by the self-assembly of different components in a one pot reaction. Thus, we have been able to isolate a water soluble heterometallic complex based on thiophenal linkage named [LnPt\(_2\)]Cl\(_2\). The complex has a relatively weak lanthanide luminescence, which increases upon addition of DNA. Photophysical and DNA binding properties of the lanthanide-platinum complex were investigated by UV-vis absorption, luminescent studies and circular and linear dichroism. Oligonucleotides of twelve bases were also used to investigate the intercalation [LnPt\(_2\)]Cl\(_2\) and the mono-intercalator AATP used as control compound. Using bidimensional NMR techniques, we investigated the binding site for [LnPt\(_2\)]Cl\(_2\) and AATP upon interaction with Dickerson-Drew sequence. The sulphur lanthanide-platinum linkage in [LnPt\(_2\)]Cl\(_2\) was replaced with an acetylide one in order to introduce new photophysical features. Thus the self-assembly procedures based on DTPA-bis(amido-acetylide) and a platinum(II) terpyridine led us to isolate a new lanthanide-platinum complex named [LnC\(\equiv\)CPt\(_2\)] (CH\(_3\)SO\(_3\))\(_2\). The photophysical properties and the DNA binding properties toward interaction with CT-DNA were investigated. The complex named LnC\(\equiv\)CPt\(_2\)](CH\(_3\)S)\(_3\))\(_2\) exhibited a relatively strong lanthanide luminescence that increased upon addition of DNA. The bi-functional metal complex [EuLPt](PF\(_6\)) (where Pt=platinum-2,2':6'2"-terpyridine and L=assymmetric DTPA bisamide ligand with a thiopheno pendant arm and a quinoline moiety) was synthesised and the interaction of [EuLPt](PF\(_6\)) with CT-DNA was examined by luminescence spectroscopy, linear and circular dichroism studies and thermal denaturation studies. The [EuLPt](PF\(_6\)) retained the ability to increase its luminescence upon the addition of CT-DNA. The binding properties of the complexes were tested toward interaction with plasmid DNA by gel electrophoresis and properties such as the unwinding angle were measured. The bis-intercalators [LnPt\(_2\)]Cl\(_2\) and [LnC\(\equiv\)CPt\(_2\)](CH\(_3\)SO\(_3\))\(_2\) showed the ability to uncoil DNA almost as well as cisplatin and at low concentrations, while almost double the amount of mono-intercalators, such as [EuLPt](PF\(_6\)) is required to observe the same uncoiling effect.
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White, Jenifer Christine. "Novel functionalised, nanoarrays of DNA binding supramolecular helicates." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6625/.
Повний текст джерелаАнотація:
Work described in this thesis shows the design, synthesis, DNA binding activity and gold nanoparticle interaction of functionalised triple stranded supramolecular helicates. DNA structures and the way molecules recognise and bind to them are reviewed, with specific emphasis on supramolecular compounds. Supramolecular helicates are discussed in detail with consideration of how they may be used as anticancer agents. Nanoparticles, specifically gold nanoparticles are studied, with specific reference to how they are able to enhance anticancer properties of drug molecules and how they may be used to develop potent anticancer therapies. With the formation of three novel supramolecular iron helicates and the incorporation of supramolecular chemistry and nanotechnology, through binding such complexes to the surface of gold nanoparticles, foundations of work in this area are discussed, showing promising results for future research.
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Brown, Bronwen Marylouise. "P22 arc--energetics and cooperativity of DNA binding." Thesis, Massachusetts Institute of Technology, 1994. http://hdl.handle.net/1721.1/33491.
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