Tyrosine Analogs

In an analogous vein to serine/threonine protein kinases, peptide-based inhibitors of tyrosine kinases were initially prepared by substituting the phos-phorylatable tyrosine with the nonphosphorylatable phenylalanine. In general, the phenylalanine-for-tyrosine replacement generates exceedingly poor inhibitory agents (Ki>1 mM).

Several peptides containing tyrosine analogs (12-14) were reported in the 1980s, but these derivatives proved to be ineffective as inhibitors (Wong and Goldberg 1984; Shoelson et al. 1989).

Graves and his colleagues described the first example of an effective pep-tide-based tyrosine kinase inhibitor (Yuan et al. 1990).

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