Reductive Electron Transfer in DNA

With regard to important biological consequences such as DNA damage, mutagenesis, and carcinogenesis, in most of the experiments described above only oxidative HT processes have been observed. As shown in the Sections 4.6.1 and 4.6.2, such HT results in oxidative G damage at remote sites on the nucleic acid. On the other hand, reductive electron transfer (ET) processes (Figure 4.6.7) are currently used in DNA chip technology 22 and DNA nanotechnology 23 . Despite broad knowledge about these...

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Molecular motion feasible in rotaxanes (top) and catenanes (bottom). ping by two bulky stopper groups that mechanically trap the axle. Consequently, the axle is free to move inside the wheel, because there is no covalent bond between the two components. Several different types of motion are feasible. Besides rotation of the axle inside the wheel, the wheel can move back and forth along the axle, if it is long enough. This process can be regarded as one-dimensional diffusion along...

Spiegelmer Technology

First, a target molecule for which an antagonist is desired is identified. If this target molecule is a peptide, the sequence is synthesized in the synthetic mirror image configuration. Standard methods of synthesis, for example Fmoc or Boc chemistry (Box 25), can be employed using d amino acid building blocks 16 . If the target is a bigger protein it is useful to define epitopes or domains of that protein which can be synthesized in the mirror image configuration. By also using peptide...

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These results imply that the functional l-RNA and d-RNA sequences are folding into mirror-image shapes this is consistent with the observed circular dichroism (CD) spectra of the functional 58-mer RNA sequences. CD spectra were recorded in 0.1 M NaCl and 10 mM sodium phosphate, pH 7.0, at 4 C on a Jasco J-600 spectropolarimeter. Fig. 3.4.5. Biological stability of an aptamer (d-oligonucleotide) and a spiegelmer (l-oligonucleotide) in human serum. Both oligonucleotides were incubated in buffered...

Oxidations with Immobilized Periodinanes

In recent years hypervalent iodine compounds have experienced extensive investigations yielding many results of practical synthetic importance. Supported iodi-nanes, i.e. iodoso or iodine(III) reagents, have been prepared by several groups, mainly as the bis-acetoxyiodoso derivatives 15-18 or as the respective dihalogeno compounds 19 . Iodoso reagents are employed in the oxidation of hydroquinones and phenols that have been exploited in the formation of spiroketals from a variety of tyrosines....

Introduction

''Alzheimer's disease (AD) is a devastating illness that robs humans of their ability to remember, to think and to understand all the things we cherish most about being human.'' (P.F. Chapman) Alzheimer's disease (AD) is an epidemic neurodegenerative disorder claiming millions of victims per year. The aging of the world population will be accompanied by an even higher toll. According to the World Health Organization the prevalence of Alzheimer's disease is 5.5 above 60 years of age and...

Genetic Selection of an Errorprone Variant of Bacteriophage T7 RNA Polymerase

Bacteriophage

Studies with several RNA viruses have demonstrated their exceptionally high replication error rates that confer genetic flexibility, while resulting in substantial decreases of infectivity 35, 36 . Enhanced mutagenesis might even result in virus extinction, as predicted from virus entry into an ''error catastrophe'' 37, 38 . We are interested in studying and utilizing the link between error-prone polymerases and virus viability and started our search for an error-prone variant with the RNA...

Hemoglobin and Myoglobin

Hemoglobin, the constituent of red blood cells responsible for transport of dioxygen, and myoglobin, present in skeletal muscles to store dioxygen, are probably the most thoroughly studied proteins. Hemoglobins were first found in blood because of their very high concentration 15 g per 100 mL in normal human blood . Until recently it seemed that the oxygen carrier function was so specialized that it appeared to be the only role of these Scheme B.10.1. The active site of hemoglobin and...

Spiegelmers Binding to Small Molecules

Spiegelmers

The first functional mirror-image oligonucleotides, spiegelmers, described in 1996 were generated to bind to small molecules, i.e. the amino acid arginine and the nucleoside adenosine 18, 19 . For in-vitro selection against adenosine, the target in the enantiomeric configuration was covalently coupled to a matrix. A standard characterized and tested for binding to the mirror-image form of the naturally occurring target. The sequences of identified binders are then synthesized in the...

The NOmediated Reduction of FerrylMb and FerrylHb

It has been suggested that heme-mediated redox reactions contribute to the organ dysfunction and or tissue damage which occur in some pathological states characterized by release of Hb and Mb into the extracellular environment 29 . Autoxidation of oxyHb and oxyMb to their met-forms releases superoxide which dis-mutates to dioxygen and hydrogen peroxide, which in turn can cause tissue damage 30 . In addition, oxidation of these two proteins generates potentially cy-totoxic products such as the...