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Author: Fadwa Dhafer Hamad Publisher: ISBN: Category : DNA-binding proteins Languages : en Pages : 114
Book Description
DNA-drug interactions play a major role in therapeutics, diagnostics, forensics and imaging. Drugs bind to DNA in several ways based on the mode of interaction and they alter protein-DNA interactions or breaks/cleaves DNA that can lead to the cure of the disease. The major goal of the research carried out in this thesis is to develop novel optical spectroscopic tools that can differentiate Drug-DNA binding interactions mode whether its intercalation or minor-groove binding. To achieve this goal, we developed two-photon absorption (2PA) cross-section based technique to differentiate between Drug-DNA binding modes. The investigations were carried out on two drug molecules, DAPI and Thiazole Orange (ThO) binding to Salmon Sperm-DNA and Calf Thymus-DNA. DAPI binds to the DNA via minor-groove while ThO intercalates with DNA. Relative 2PA cross-section studies have shown about 3-fold enhancement for DAPI whereas ThO has shown no enhancement. These results confirmed our hypothesis. To further establish this method, studies were carried out using two more drug molecules, Netropsin and Doxorubicin with Salmon Sperm-DNA. Netropsin is a non-fluorescent drug that required a marker to read its binding interaction with DNA. Two types of markers have been used, Hoechst-33258 was used as minor-groove marker and Thioflavine T as intercalator. Doxorubicin drug is fluorescent and the binding results via the 2PA cross-sections have shown a slight decrease in 2PA-fluorescence, suggesting the intercalation binding mode with DNA.
Author: Fadwa Dhafer Hamad Publisher: ISBN: Category : DNA-binding proteins Languages : en Pages : 114
Book Description
DNA-drug interactions play a major role in therapeutics, diagnostics, forensics and imaging. Drugs bind to DNA in several ways based on the mode of interaction and they alter protein-DNA interactions or breaks/cleaves DNA that can lead to the cure of the disease. The major goal of the research carried out in this thesis is to develop novel optical spectroscopic tools that can differentiate Drug-DNA binding interactions mode whether its intercalation or minor-groove binding. To achieve this goal, we developed two-photon absorption (2PA) cross-section based technique to differentiate between Drug-DNA binding modes. The investigations were carried out on two drug molecules, DAPI and Thiazole Orange (ThO) binding to Salmon Sperm-DNA and Calf Thymus-DNA. DAPI binds to the DNA via minor-groove while ThO intercalates with DNA. Relative 2PA cross-section studies have shown about 3-fold enhancement for DAPI whereas ThO has shown no enhancement. These results confirmed our hypothesis. To further establish this method, studies were carried out using two more drug molecules, Netropsin and Doxorubicin with Salmon Sperm-DNA. Netropsin is a non-fluorescent drug that required a marker to read its binding interaction with DNA. Two types of markers have been used, Hoechst-33258 was used as minor-groove marker and Thioflavine T as intercalator. Doxorubicin drug is fluorescent and the binding results via the 2PA cross-sections have shown a slight decrease in 2PA-fluorescence, suggesting the intercalation binding mode with DNA.
Author: Saad Hmoud Alotaibi Publisher: ISBN: Category : Languages : en Pages : 325
Book Description
The discovery of DNA as a genetic material and its double helical structure led to numerous studies directed at understanding molecule-DNA interactions. These studies have played an integral role in medical diagnostics, forensics, imaging and therapeutics. Typically, molecule-DNA interactions have two prominent modes: intercalation and minor groove binding. Several optical techniques are available that can monitor molecule-DNA binding interactions, but they cannot differentiate between intercalation and minor-groove binding. The major goals of the research are to develop novel optical spectroscopic tools that can differentiate molecule-DNA binding interactions, selectively and sensitively detect one form of DNA over another, and track DNA melting curves. To accomplish these goals, we developed two-photon absorption (2PA) cross-section based techniques to differentiate between molecule-DNA binding interactions. The hypothesis is that the 2PA cross-sections of molecules are sensitive to the electrostatic fields offered by the DNA backbone and that the alignment of molecular dipoles with the electric field can differentiate the mode of binding. To test the hypothesis, investigations were carried out using two dye molecules, Hoechst 33258 (Hoe) and Acridine Orange (AcrO) binding to DNA. Hoe binds to the DNA via minor groove while AcrO intercalates with DNA. Relative 2PA cross-section studies have shown a more than 4-fold enhancement for Hoe whereas AcrO has no enhancement. These results confirmed our hypothesis that 2PA cross-sections of dye molecules are sensitive to local electric fields and that they can differentiate molecule-DNA interactions. This technique was extended to monitoring the interaction of other prominent dye molecules (like Thioflavin T and cyanine dyes) with DNA, and the technique was successful in elucidating the mode of binding in these systems. Also, one-, two-photon fluorescence sensing and relative 2PA cross-sections of dye molecules were used as markers to differentiate between single-stranded, duplex and G-quadruplex DNA structures. We have also used the power of 2PA cross-sections to track DNA melting transitions in duplex and quadruplex structures. Furthermore, a novel two-photon based induced fluorescence resonance energy transfer (2P-iFRET) technique was developed to monitor the DNA melting. Results have shown that this technique is sensitive and offers flexibility and sharper melting transitions over conventional techniques.
Author: Kazuo Nakamoto Publisher: John Wiley & Sons ISBN: 0470369167 Category : Science Languages : en Pages : 475
Book Description
Learn vital information about drug-DNA interactions from Drug-DNA Interactions: Structures and Spectra, the only comprehensive book written about this topic. Understand the types of structural and bonding information that can be obtained using specific physico-chemical methods and discover how to design new drugs that are more effective than current treatments and have fewer side effects. Find detailed information about X-ray crystallography, NMR spectroscopy, molecular modeling, and optical spectroscopy such as UV-Visible absorption, fluorescence, circular dichroism (CD), flow linear dichroism (FLD), infrared (IR) and Raman spectroscopy.
Author: Publisher: BoD – Books on Demand ISBN: 1789840473 Category : Science Languages : en Pages : 112
Book Description
Biophysical chemistry is one of the most interesting interdisciplinary research fields. Some of its different subjects have been intensively studied for decades. Now the field attracts not only scientists from chemistry, physics, and biology backgrounds but also those from medicine, pharmacy, and other sciences. We aimed to start this version of the book Biophysical Chemistry from advanced principles, as we include some of the most advanced subject matter, such as advanced topics in catalysis applications (first section) and therapeutic applications (second section). This led us to limit our selection to only chapters with high standards, therefore there are only six chapters, divided into two sections. We have assumed that the interested readers are familiar with the fundamentals of some advanced topics in mathematics such as integration, differentiation, and calculus and have some knowledge of organic and physical chemistry, biology, and pharmacy. We hope that the book will be valuable to graduate and postdoctoral students with the requisite background, and by some advanced researchers active in chemistry, biology, biochemistry, medicine, pharmacy, and other sciences.
Author: Kazuo Nakamoto Publisher: Wiley ISBN: 9780471786269 Category : Science Languages : en Pages : 392
Book Description
Learn vital information about drug-DNA interactions from Drug-DNA Interactions: Structures and Spectra, the only comprehensive book written about this topic. Understand the types of structural and bonding information that can be obtained using specific physico-chemical methods and discover how to design new drugs that are more effective than current treatments and have fewer side effects. Find detailed information about X-ray crystallography, NMR spectroscopy, molecular modeling, and optical spectroscopy such as UV-Visible absorption, fluorescence, circular dichroism (CD), flow linear dichroism (FLD), infrared (IR) and Raman spectroscopy.
Author: Klaus Wanner Publisher: John Wiley & Sons ISBN: 3527314563 Category : Science Languages : en Pages : 463
Book Description
This first overview of mass spectrometry-based pharmaceutical analysis is the key to improved high-throughput drug screening, rational drug design and analysis of multiple ligand-target interactions. The ready reference opens with a general introduction to the use of mass spectrometry in pharmaceutical screening, followed by a detailed description of recently developed analytical systems for use in the pharmaceutical laboratory. Applications range from simple binding assays to complex screens of biological activity and systems containing multiple targets or ligands -- all highly relevant techniques in the early stages in drug discovery, from target characterization to hit and lead finding.
Author: Bernhard Lippert Publisher: John Wiley & Sons ISBN: 9783906390208 Category : Medical Languages : en Pages : 628
Book Description
30 years after its discovery as an antitumor agent, cisplatin represents today one of the most successful drugs in chemotherapy. This book is intended to reminisce this event, to take inventory, and to point out new lines of development in this field. Divided in 6 sections and 22 chapters, the book provides an up-to-date account on topics such as - the chemistry and biochemistry of cisplatin, - the clinical status of Pt anticancer drugs, - the impact of cisplatin on inorganic and coordination chemistry, - new developments in drug design, testing and delivery. It also includes a chapter describing the historical development of the discovery of cisplatin. The ultimate question - How does cisplatin kill a cell? - is yet to be answered, but there are now new links suggesting how Pt binding to DNA may trigger a cascade of cellular reactions that eventually result in apoptosis. p53 and a series of damage recognition proteins of the HMG-domain family appear to be involved. The book addresses the problem of mutagenicity of Pt drugs and raises the question of the possible relevance of the minor DNA adducts, e.g. of interstrand cross-links, and the possible use of trans-(NH3)2Pt(II)-modified oligonucleotides in antisense and antigene strategies. Our present understanding of reactions of cisplatin with DNA is based upon numerous model studies (from isolated model nucleobases to short DNA fragments) and application of a large body of spectroscopic and other physico-chemical techniques. Thanks to these efforts there is presently no other metal ion whose reactions with nucleic acids are better understood than Pt. In a series of chapters, basic studies on the interactions of Pt electrophiles with nucleobases, oligonucleotides, DNA, amino acids, peptides and proteins are reported, which use, among others, sophisticated NMR techniques or X-ray crystallography, to get remarkable understanding of details on such reactions. Reactivity of cisplatin, once bound to DNA and formerly believed to be inert enough to stay, is an emerging phenomenon. It has (not yet) widely been studied but is potentially extremely important. Medicinal bioinorganic chemistry - the role of metal compounds in medicine - has received an enormous boost from cisplatin, and so has bioinorganic chemistry as a whole. There is hardly a better example than cisplatin to demonstrate what bioinorganic chemistry is all about: The marriage between classic inorganic (coordination) chemistry and the other life sciences - medicine, pharmacy, biology, biochemistry. Cisplatin has left its mark also on areas that are generally considered largely inorganic. The subject of mixed-valance Pt compounds is an example: From the sleeping beauty it made its way to the headlines of scientific journals, thanks to a class of novel Pt antitumor agents, the so-called "platinum pyrimidine blues". In the aftermath diplatinum (III) compounds were recognized and studies in large numbers, and now an organometalic chemistry of these diplatinum (III) species is beginning to emerge. The final section of the book is concerned with new developments such as novel di- and trinuclear Pt(II) drugs with DNA binding properties different from those of cisplatin, with orally active Pt(IV) drugs which are presently in clinical studies, and with attempts to modify combinatorial chemistry in such a way that it may become applicable to fast screening of Pt antitumor drugs. The potential of including computational methods in solving questions of Pt-DNA interactions is critically dealt with in the concluding chapter.
Author: Fadwa Dhafer Hamad
Author: Fadwa Dhafer Hamad
Author: Saad Hmoud Alotaibi
Author: Kazuo Nakamoto
Author: 
Author: Catherine Anna Butler
Author: Lee Walters
Author: Kazuo Nakamoto
Author: Klaus Wanner
Author: Bruce Alberts
Author: Bernhard Lippert