Chemical synthesis of 4-azido-β-galactosamine derivatives for inhibitors of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase
Chemical synthesis of 4-azido-β-galactosamine derivatives for inhibitors of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase
复制标题
用于N-乙酰半乳糖胺4-硫酸盐6-O-磺基转移酶抑制剂的4-叠氮基-β-半乳糖胺衍生物的化学合成
DOI：
10.1007/s10719-018-9839-2
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发表时间：
2018
影响因子：
3
通讯作者：
Nakano Hirofumi
中科院分区：
文献类型：
--
作者：
Hor Seanghai;Kodama Takumi;Sugiura Nobuo;Kondou Hikaru;Yanagida Mio;Yanagisawa Keiya;Shibasawa Aoki;Tsuzuki Bunta;Fukatsu Naoto;Nagao Kazuya;Yamana Kenji;Hidari Kazuya I. P. J.;Watanabe Hideto;Habuchi Osami;Nakano Hirofumi
硫酸软骨素E（CS-E）在从病毒感染到神经再生的各种过程中起着至关重要的作用。由N-乙酰半乳糖胺4-硫酸6-O-磺基转移酶（GalNAc 4S-6ST）产生的区域特异性硫酸化模式是其生物活性的主要结构决定因素。GalNAc 4S-6ST的抑制剂可以作为理解CS-E的生理功能及其对人类疾病的潜在治疗线索的有力工具。合成了一系列新的4-酰氨基-β-GalNAc衍生物和4-叠氮基-β-GalNAc衍生物，以作为GalNAc 4S-6ST的潜在抑制剂。评价目标化合物对GalNAc 4S-6ST的抑制活性。结果表明，4-新戊酰氨基-和4-叠氮基-β-GalNAc衍生物对GalNAc 4S-6ST具有明显的抑制活性，IC 50值为0.800 ~ 0.828 mM。它们显示出比用作对照的苄基D-GalNAc 4S更高的活性。
Chondroitin sulfate E (CS-E) plays a crucial role in diverse processes ranging from viral infection to neuroregeneration. Its regiospecific sulfation pattern, generated byN-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), is the main structural determinant of its biological activity. Inhibitors of GalNAc4S-6ST can serve as powerful tools for understanding physiological functions of CS-E and its potential therapeutic leads for human diseases. A family of new 4-acylamino-β-GalNAc derivatives and 4-azido-β-GalNAc derivatives were synthesized for their potential application as inhibitors of GalNAc4S-6ST. The target compounds were evaluated for their inhibitory activities against GalNAc4S-6ST. The results revealed that 4-pivaloylamino- and 4-azido-β-GalNAc derivatives displayed evident activities against GalNAc4S-6ST with IC50value ranging from 0.800 to 0.828 mM. They showed higher activities than benzyl D-GalNAc4S that was used as control.