Wu Yanfen, Zhao Ming, Wang Chao, Peng Shiqi
College of Pharmaceutical Chemistry, Peking University, Beijing, PR China.
Bioorg Med Chem Lett. 2002 Sep 2;12(17):2331-3. doi: 10.1016/s0960-894x(02)00403-1.
Two kinds of linkers consisting of 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, ARPAK, GRPAK and QRPAK were synthesized. The thrombolytic activities in vivo indicated that the coupling position of 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in the peptides effected on the potencies significantly. When the C-terminal of the peptides was amidated by 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, the thrombolytic potency of the peptides was enhanced or kept. When the N-terminal of the peptides was acylated by 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, however, the thrombolytic effect of the peptides was banished. The expected specific beta II'-turn conformation and the stability to trypsin in the pseudopeptides with 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in its C-terminal may be responsible for the enhanced thrombolytic potency.
合成了两种由3-(S)-1,2,3,4-四氢-β-咔啉-3-羧酸、ARPAK、GRPAK和QRPAK组成的连接体。体内溶栓活性表明，3-(S)-1,2,3,4-四氢-β-咔啉-3-羧酸在肽中的偶联位置对效力有显著影响。当肽的C末端被3-(S)-1,2,3,4-四氢-β-咔啉-3-羧酸酰胺化时，肽的溶栓效力增强或保持。然而，当肽的N末端被3-(S)-1,2,3,4-四氢-β-咔啉-3-羧酸酰化时，肽的溶栓作用消失。在其C末端含有3-(S)-1,2,3,4-四氢-β-咔啉-3-羧酸的拟肽中预期的特定β II'-转角构象和对胰蛋白酶的稳定性可能是溶栓效力增强的原因。
