腺嘌呤核?、胞嘧啶核?及石膽酸衍生物的合成及生物活性評估

李榮展

指導教授 ： 李文山

國立臺灣師範大學/理學院/化學系/碩士(2004年)

摘要

無資料

關鍵字

唾液酸 ； 核醣 ； 石膽酸 ； 核酸 ； 抑制劑

並列摘要

Carbohydrates not only involved in cell-cell recognition, message
transfer but the energy supplement. Sialic acid is one of the carbohydrates
and plays important roles in human physiology. Sialyltransferase can
catalyze sialic acid(SA) transfer from SA donor to SA acceptor. In recent
researches, we found that the expression of SA is correlated with cancer
cells. In patients’tumor cell, there is a great increase in activities of
sialyltransferases.We tried to synthesize the inhibitor of sialyltransferase
,and modified the substructure of adenosine , cytidine and lithocholic acid (LA) respectively. These compounds to were tested their inhibitory properties for α(2→3)sialyltransferase.For the first part, we were successful in synthesizing 5´-deoxy- cytidine monophosphate by 11 steps, and the total yield is about 0.5% .The activity of 5´-deoxy- cytidine monophosphate is lower than CMP, We found 5´-oxygen atom may serve as a role to produce hydrogen bonding with amino acid residue at the active site of the enzyme. The binding affinity between ligand-enzyme is probably terminated because it is absence of oxygen atom.This should result in the reduction of inhibitory potential of 5´-deoxy- cytidine monophosphate toward α(2→3)sialyltransferase. For the second part, the inhibition of derivatives from modified cytidine and adenosine is about mM range.The base in nucleosides may not be the major responsibility for inhibition. For the third part, we took K. Barry Sharpless’method to catalyze the reaction of terminal alkyne and azide ,then six derivatives from LA with good inhibition were successfully synthesized. We found that these triazole cpds. with a terminal carboxyl group have the best inhibition to α(2→3)sialyltransferase, the triazole compounds of LA . with a branched aromatic functional group or terminal hydroxyl group will decrease inhinition potential.