Download Methods for Studying Nucleic Acid/Drug Interactions by Meni Wanunu, Yitzhak Tor PDF

By Meni Wanunu, Yitzhak Tor

Since so much healing efforts were predominantly keen on prescribed drugs that focus on proteins, there's an unmet have to enhance medicines that intercept mobile pathways that significantly contain nucleic acids. development within the discovery of nucleic acid binding medicinal drugs evidently will depend on the supply of analytical equipment that investigate the efficacy and nature of interactions among nucleic acids and their putative ligands. This development can gain drastically from new equipment that probe nucleic acid/ligand interactions either speedily and quantitatively.

A number of novel equipment for those experiences have emerged lately, and Methods for learning DNA/Drug Interactions highlights new and non-conventional equipment for exploring nucleic acid/ligand interactions. Designed to provide drug-developing businesses with a survey of attainable destiny recommendations, the ebook compares their drawbacks and benefits with recognize to customary instruments. might be extra importantly, this ebook used to be written to motivate younger scientists to proceed to develop those equipment into fruition, particularly in gentle of present features for assay miniaturization and better sensitivity utilizing microfluidics and nanomaterials.

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1 Interactions between Metal Complexes and Duplex DNA ESI-MS has been able to effectively show covalent binding of cisplatin to DNA and that sequence selectivity can be determined. This is partly because when a metal complex binds to dsDNA, it shields the nearby phosphodiester bonds from enzymatic hydrolysis. 139 Efforts to examine noncovalent-binding interactions with dsDNA using ESI-MS employed classical organic minor groove-binding agents, intercalators, and some metal complexes, including several sterically hindered metalloporphyrins and [Ru(12S4)(dppz)]2+ (12S4 = 1,4,7,10-tetrathiatetradecane).

The imino protons in the Watson–Crick base pairs 1 16 Methods for Studying Nucleic Acid/Drug Interactions G–C and A–T are exchanged with the solvent in pure D2O and are therefore not observed in a normal 1H NMR spectrum. 58 Disruption of the normal base pairing and/or stacking after drug binding is observed through the loss of one or more imino resonances, when compared to the unbound oligonucleotide under the same conditions. 10 Diffusion Experiments Any molecule in a solution, including drugs and DNA, will travel in a random path due to Brownian motion.

The intercalation changes the conformation of the DNA and the CD spectrum. In addition to the changes that occur due to the difference in the DNA conformation, there is an induced CD (ICD) signal that arises from the ligand. CD is a sensitive probe of changes in biomacromolecular structure and may be used to probe DNA interactions with small molecules. This is also true with achiral molecules whose ICD is solely due to their interaction with DNA. 13 The absorbance (a), circular dichroism spectra (b) of ct-DNA (the solid black line indicates initial B-type DNA conformation) with increasing concentration of the intercalator [Pt(phen)(en)]2+, and the induced circular dichroism spectra (c) showing the net effect of intercalation on DNA.

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