Solid-phase synthesis of (tyrosyl-alanyl-glutamyl)n, by segment condensation

(Tyr‐Ala‐Glu)n, n= 1–9, were synthesized by segment condensation using 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‐r‐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 Fnioc‐Glu(0‐t‐Bu) to the growing chain. Neither sequential amino acid addition or segment condensation techniques were successful on polystyrene supports. However, the segment condensations were highly successful on kieselguhr‐supported polydimethylacrylamide based resins. (Tyr‐Ala‐Glu)n, n= 1–9, were tested as inhibitors of the protein [yosine kinase, pp60Cc‐src. Inhibition, as measured by IC50 values, increased with increasing size of the peptide.