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...

Invivo Data of GnRH Binding Spiegelmers

To increase the affinity and improve the temperature-stability of the anti-GnRH DNA sequence the original in-vitro selection was re-initiated after the first selection stage. The selection procedure was therefore performed at 37 C and with greater stringency. After nine additional cycles of selection and amplification the fraction that bound to D-GnRH was increased to 13 . Enriched molecules of the tenth cycle were cloned and sequenced. Thirty-eight out of 48 sequences contained a clone that...

Proline synanti Isomerization Implications for Protein Folding

Syn-anti isomerization N-terminal to prolyl peptide fragments is one of the rate limiting steps in protein folding 1 . Prolyl fragments exist essentially either in the syn or anti form in native proteins, but as an equilibrium mixture of these two rotamers in unfolded proteins and small peptides. These two conformational states are almost isoenergetic see Figure 1.2.3 for comparison , with the anti form being slightly more favorable. Both rotamers are separated by a significant energy barrier...

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...

Spiegelmers Binding to Small Molecules

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...

References

1 See, for example, selected excellent reviews and references cited therein a i. Haq, j. Ladbury, J. Mol. Recognit. 2000, 13, 188-197 b p. b. Dervan, r. w. BUrli, Curr. Opin. Chem. Biol. 1998, 3, 688-693 c w. d. Wilson, Nucleic Acids in Chemistry and Biology, g. m. Blackburn, m. j. Gait, eds., IRL Press, Oxford, UK, 1996, pp. 329-374 d b. h. Geierstanger, d. e. Wemmer, Annu. Rev. Biophys. Biomol. Struct. 1995, 24, 463-493 e Recent Advances in DNA Binding Agents. Symposia in print number 4,...

Bi2

Taxus brevifolia T. ba. Taxus baccata C. v. Cortinarius violaceus B. b. Bacillus brevis Vm4 a Involvement of B12 is unlikely bAn 15 N label in tyrosine is lost in the product -tyrosine laceus. These enzymes are unlikely to use B12. These enzymes have, on the other hand, not yet been isolated nor investigated in detail, so their classification remains speculative. The tyrosine 2,3-aminomutase of Bacillus brevis Vm4 differs fundamentally from all the...

Info

B-Amino acids have been found within secondary and primary metabolism of all kingdoms. Although quantitative ranking is tricky, at this point bacteria seem to be the most active ''b-amino acid chemists'', followed by fungi, plants, and animals we exclude protists from this grading list as a consequence of their lower examination status. A natural b counterpart has not yet been obtained for every proteinogenic a-amino acid Table 1.5.1 . b-Ala 1 and R - or S -b-Aib 2 seem to be present in all...

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...

List of Contributors

Institut fur Organische Chemie RWTH- Aachen Professor-Pirlet-Stra e 1 52074 Aachen Germany Ruprecht-Karls-Universitat Heidelberg Institut fUr Pharmazie und Molekulare Biotechnologie Im Neuenheimer Feld 364 69120 Heidelberg Germany Research Unit ''Enzymology of Protein Folding'' Weinbergweg 22 06120 Halle Saale Germany Ruhr-Universit t Bochum Fakultat fur Chemie 44780 Bochum Germany Institut fur Organische Chemie Universitat Karlsruhe TH Fritz-Haber-Weg 6 76131 Karlsruhe Germany Institut fur...

Basf Ag

Research Fine Chemicals GVF E -A30 67056 Ludwigshafen Germany Ecole Polytechnique F d rale de Lausanne EPFL Institut des Materiaux, Laboratoire des Polym res Batiment MX-D, 1015 Lausanne Switzerland NOXXON Pharma AG Max-Dohrn-Stra e 8-10 10589 Berlin Germany Kekule-Institut fur Organische Chemie und Biochemie der Rheinischen Friedrich-Wilhelms-Universitat Bonn Gerhard-Domagk-Strasse 1 53121 Bonn Germany Max Planck Institute of Molecular Physiology Address Otto-Hahn-Stra e 11 44227 Dortmund...