Obeyesekere N U, La Croix J N, Budde R J, Dyckes D F, McMurray J S
Department of Neuro-Oncology, University of Texas, M.D. Anderson Cancer Center, Houston.
Int J Pept Protein Res. 1994 Feb;43(2):118-26. doi: 10.1111/j.1399-3011.1994.tb00512.x.
(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-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 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 tyrosine kinase, pp60c-src. Inhibition, as measured by IC50 values, increased with increasing size of the peptide.
采用Fmoc/叔丁基保护策略和固相技术，通过片段缩合合成了n = 1 - 9的(Tyr - Ala - Glu)n。将C末端残基偶联到树脂上，通过添加Fmoc - Glu(O - t - Bu) - Tyr(t - Bu) - Ala - OH单元来构建肽段。当达到所需长度时，用Fmoc - Tyr(t - Bu) - Ala - OH单元对肽段进行封端。通过将Fmoc - Tyr(t - Bu)和Fmoc - Glu(O - t - Bu)的N - 羟基琥珀酰亚胺酯依次添加到增长链中，在水溶液中合成了Fmoc - Tyr(t - Bu) - Ala - OH和Fmoc - Glu(O - t - Bu) - Tyr(t - Bu) - Ala - OH。在聚苯乙烯载体上，连续氨基酸添加或片段缩合技术均未成功。然而，在硅藻土负载的聚二甲基丙烯酰胺基树脂上，片段缩合非常成功。对n = 1 - 9的(Tyr - Ala - Glu)n作为蛋白酪氨酸激酶pp60c - src的抑制剂进行了测试。通过IC50值衡量的抑制作用随肽段大小的增加而增强。
