POTENTIAL MECHANISM-BASED TYROSINE KINASE INHIBITORS .2. DESIGN AND SYNTHESIS OF PEPTIDES CONTAINING HETEROCYCLIC TYROSINE ANALOGS

The Fmoc derivatives of two homochiral tyrosine analogues, a pyridine N-oxide and a pyridone, have been prepared in high stereochemical puri ty. Solid-phase synthesis has been used to prepare a decapeptide subst rate for the tyrosine kinase domain of epidermal growth factor. Two de capeptides, which incorporate the tyrosine analogues in place of tyros ine, and thereby have the potential to act as mechanism-based inhibito rs of epidermal growth factor tyrosine kinase, have been synthesised a nd found to inhibit the aforementioned kinase.