|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1998 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1997 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Extracts from sea urchin were screened for new anti-tumor drugs. Two glycolipids, 3'-sulfowuinovosyl-1', 2'diacylglyceride and monoacylglycerude were isolated and characterized by means of spectrometric analyses. When tested for cytotoxic activity against tumor cells in vitro, monoacylate showed significant activity, however, it was still including saturated and unsaturated lipids onC-1' orC-2'. This project aimed to detemine acute active structure and evaluate their cytotoxity. Starting from alpha-allylglucopyranoside, targeted molecules were successfully synthesized. Depending on lipids moiety, over 20 compounds were obtained. In a similar manner, beta-analogues were also synthesized from beta-allylglucopyranoside. Based on mammalian DNA polymerase assay, some compounds showed excellent enzymatic inhibition. Now we look toward their possibility for clinical use.
The biochemical analysis clarified that lipid birds 8kDa domain of DNA polymerase beta. N15 enriched 8kDa protein was obtained from a cloned bacteria. The isolated protein and lipid were served for 750MHzNMR analysis. From combined NMR data and computer molecular modeling, we determined that the birding site of lipid with 8kDa domain of DNApo1ymerasebeta should be L11, K35, H51 and T79 amino residue.