SOLID-PHASE SYNTHESIS OF (TYROSYL-ALANYL-GLUTAMYL)(N) BY SEGMENT CONDENSATION

(Tyr-Ala-Glu)(n), n=1-9, were synthesized by segment condensation usin g the Fmoc/tert-butyl protection strategy and solid-phase techniques. The C-terminal residue was coupled to the resin and the peptides were built out by adding Fmoc-Glu(O-t-Bu)-Tyr(t-Bu)-Ala-OH units. When the desired lengths were reached the peptides were capped with Fmoc-Tyr(t- Bu)-Ala-OH units. Fmoc-Tyr(t-Bu)-Ala-OH and Fmoc-Glu(O-t-Bu)Tyr(t-Bu)- Ala-OH were synthesized in aqueous solution by the successive addition of N-hydroxysuccinimide esters of Fmoc-Tyr(t-Bu) and Fmoc-Glu(O-t-Bu) to the growing chain. Neither sequential amino acid addition or segme nt condensation techniques were successful on polystyrene supports. Ho wever, the segment condensations were highly successful on kieselguhr- supported polydimethylacrylamide based resins. (Tyr-AlaGlu)(n), n=1-9, were tested as inhibitors of the protein tyrosine kinase, pp60(c-src) . Inhibition, as measured by IC50 values, increased with increasing si ze of the peptide. (C) Munksgaard 1994.