Bioorganic Chemistry of Biological Signal Transduction by Herbert Waldmann, G. Dorman, P.J. Hergenrother, C. Herrmann,

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 themes mentioned are very important to fields corresponding to biology, biochemistry, medicinal chemistry, and artificial natural chemistry. this article is additionally to be had electronically at an internet tackle provided with the textual content.

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1 Phosphotyrosine Mimetics The hydrolytic accessibility of the ester bond in pTyr 1 (Scheme 1) to cellular protein-tyrosine phosphatases motivated numerous research groups to develop phosphatase-resistant bioisosteric analogues. It was soon recognized that the Peptidomimetic SH2 Domain Antagonists for Targeting Signal Transduction 31 Scheme 1. Phosphorus-containing pTyr mimics phosphate structure itself imparts critical functionality to the tyrosine. , phenylalanine platforms has finally attracted the interest of classical peptidomimetic research.

1 X-Ray Analysis . . . . . . 2 NMR Spectroscopy . . . . . 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5 µmol/l), none of which reveals an obvious peptidic origin (Scheme 11) [163]. With these de novo designed compounds the first cycle in the iterative structure-based design application was completed and the information is further used to guide next-generation analogue design to improved levels of potency [163]. As mentioned several times throughout this contribution, the interaction of the pTyr sidechain and the Asn sidechain in pTyr+2 position of the peptide ligand have been identified as key elements for molecular recognition (see Fig.

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