Design, synthesis and biological evaluation of sialic acid derivatives with a possible inhibitory activity against specific sialyltransferases.

摘要

Sialylation at the non-reducing end of glycoconjugates is an important biological process in cellular recognitions, tumor metastases, and immune responses, which are mediated by a family of enzymes known as sialyltransferases (ST).[1,2] These proteins, localized in the Golgi apparatus, catalyze the transfer of sialic acid (Neu5Ac 1 congeners, Figure 1), in activated form (CMP-sialic acid 2, Figure 1), to the terminal portion of glycoconjugates. An alteration of the sialyltransferase activity causes the characteristic composition of glycoproteins in transformed cells, as shown in human colorectal cancer, breast carcinoma, leukemic cell lines, and metastatic tissues. Thus, the elevated plasma sialyltransferase activities can be used as tumor markers for the cancer diseases. Moreover, characteristic differences in the occurrence of sialic acid in healthy and diseased human have been reported.[3,4]