Pan Po-Shen, McGuire Kathleen L, McAlpine Shelli R
Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182, USA.
Bioorg Med Chem Lett. 2007 Sep 15;17(18):5072-7. doi: 10.1016/j.bmcl.2007.07.025. Epub 2007 Jul 19.
Thirty-one Sansalvamide A peptide derivatives were synthesized. (3)H thymidine inhibition assays were performed using two pancreatic cancer cell lines (PL45 and BxPC-3). Six compounds possess 140-fold increased differential selectivity for cancer cell lines over normal cell lines (WS1, skin fiberblasts) and are 140 times more active against pancreatic cancer cell lines than compounds used clinically to treat these cancers (e.g., 5-FU). Structure-activity relationship studies show the inclusion of a single N-methyl and/or d-amino acid appears to be critical for presenting the active conformation of the six San A peptide derivatives to their biological target(s).
合成了31种Sansalvamide A肽衍生物。使用两种胰腺癌细胞系（PL45和BxPC-3）进行了（3）H胸苷抑制试验。六种化合物对癌细胞系的差异选择性比正常细胞系（WS1，皮肤成纤维细胞）提高了140倍，并且对胰腺癌细胞系的活性比临床上用于治疗这些癌症的化合物（例如5-氟尿嘧啶）高140倍。构效关系研究表明，包含单个N-甲基和/或d-氨基酸似乎对于将六种San A肽衍生物的活性构象呈现给其生物靶标至关重要。
