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By Herbert Waldmann, G. Dorman, P.J. Hergenrother, C. Herrmann, J. Kuhlmann, A. Levitzki, S.F. Martin, G. Müller, M. Thutewohl, H. Waldmann

A range of the main complicated themes in bioorganic and medicinal chemistry of sign transduction. the subjects mentioned are very important to fields akin to biology, biochemistry, medicinal chemistry, and artificial natural chemistry. this article can be on hand electronically at an online deal with provided with the textual content.

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A structurally rather dissimilar pTyr mimic was developed by the Boehringer Ingelheim group, namely a triazole-dicarboxylic acid derivative 31 [130], which was shown to yield highly active Lck SH2 domain antagonists. 5 Miscellaneous Derivatives Researchers at ARIAD Pharmaceuticals described the incorporation of a 3,5dinitrotyrosine 32 into peptide inhibitors of only double-digit micromolar affinity to the SH2 domains of Syk and Src [136]. Scheme 4. Dicarboxylic acid-type pTyr mimics Peptidomimetic SH2 Domain Antagonists for Targeting Signal Transduction 37 Due to the fact that the phosphate was replaced against entirely non-charged and phosphatase-stable analogues, the pTyr mimic is considered to have more favorable pharmacokinetic properties.

62 64 64 66 66 67 70 73 73 74 75 75 77 77 77 78 78 Topics in Current Chemistry, Vol. 211 © Springer-Verlag Berlin Heidelberg 2000 62 J. Kuhlmann · C. 5 UV/Vis Spectroscopy . . . . . 6 Fluorescence-Based Assays . . . 7 Surface Plasmon Resonance . . . 8 Circular Dichroism . . . . . 2 Equilibria . . . . . . . . 2 Fluorescence Titration . . . . 3 Isothermal Titration Calorimetry . 3 Kinetic Analysis . . . . . . 1 Separation Techniques . . . . 2 Stopped Flow . . . .

4 Signal Transduction . . . . . Heterotrimeric G-Protein . . . Small GTP-Binding Proteins . . . Ras . . . . . . . . . . Membrane Anchorage . . . . GTPase Cycle . . . . . . . Effectors . . . . . . . . Relatives of Ras . . . . . . Other Members of the Ras Subfamily Rho Subfamily . . . . . . . Rab and Arf Subfamilies . . . . Ran . . . . . . . . . . 2 Biophysical Methods . . . . . . . . . . . . . 77 . . . . .

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