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f) D. Huster, K. Kuhn, D. Kadereit, H. Waldmann, K. Arnold, Angew. Chem. 2001, 113, 1083-1085;
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0142178212
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For illustrative examples that prove the importance and power of this approach for Ras and Rab proteins, see: a) A. Rak, O. Pylypenko, T. Durek, A. Watzke, S. Kushnir, L. Brunsveld, H. Waldmann, R. S. Goody, K. Alexandrov, Science 2003, 302, 646-650;
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b) O. Rocks, A. Peyker, M. Kahms, P. J. Verveer, C. Koerner, M. Lumbierres, J. Kuhlmann, H. Waldmann, A. Wittinghofer, P. I. H. Bastiaens, Science 2005, 307, 1746-1752.
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18
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0029910723
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For alternative solid-phase and solution-phase synthesis methods that meet part of the above criteria, see: a) M. Koppitz, T. Spellig, R. Kahmann, H. Kessler, Int. J. Pept. Protein Res. 1996, 48, 377-380;
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0037019977
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We have repeatedly observed that after oxidative cleavage of the hydrazide linker major fractions of the synthesized lipopeptides remained bound to the solid support by means of an unidentified linkage that could not be cleaved oxidatively or under acidic or basic conditions anymore. The oxidative cleavage of the hydrazide linker most probably proceeds through an intermediate acyl radical (see: M. Völkert, S. Koul, G. H. Müller, M. Lehnig, H. Waldmann, J. Org. Chem. 2002, 67, 6902-6910) that may form a covalent bond with the polymeric support.
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Numerous attempts to trap such an intermediate under the conditions of release from the solid support were, however, fruitless (for a related observation, see: J. A. Camarero, B. J. Hackel, J. J. de Yorco, A. R. Mitchell, J. Org. Chem. 2004, 69, 4145-4151).
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see ref. [7c]
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The compatibility of methionine and Cys(Trt) with the conditions for the cleavage of the Ellman linker has been described before, see ref. [7c]
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33
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0035896201
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Serine side chains were protected as trityl ethers, lysine side chains were masked with the methyltrityl (Mtt) group. The side-chain protecting groups were removed from the peptides by treatment with TFA/triethylsilane/ dichloromethane (1:2:97) for 2 h after the release of the peptides from the solid support (see D. Kadereit, P. Deck, I. Heinemann, H. Waldmann, Chem. Eur. J. 2001, 7, 1184-1193).
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30444438644
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note
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In further experiments, it was shown that a BODIPY fluorophore can also be introduced at the C terminus of lipidated peptides by nucleophilic trapping of the activated sulfonamide with the BODIPY-2-aminoethyl amide (data not shown).
-
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36
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