Chemical synthesis of 4-azido-β-galactosamine derivatives for inhibitors of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase

Chondroitin sulfate E (CS-E) plays a crucial role in diverse processes ranging from viral infection to neuroregeneration. Its regiospecific sulfation pattern, generated by N -acetylgalactosamine 4-sulfate 6- O -sulfotransferase (GalNAc4S-6ST), is the main structural determinant of its biological act...

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Bibliographic Details
Published in:Glycoconjugate journal 2018-10, Vol.35 (5), p.477-491
Main Authors: 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
Format: Article
Language:English
Subjects:
Amides - chemistry
Animals
Biochemistry
Biological activity
Biomedical and Life Sciences
Chondroitin sulfate
D-Galactosamine
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Galactosamine - chemical synthesis
Galactosamine - chemistry
Galactosamine - pharmacology
Humans
Inhibitors
Life Sciences
N-Acetylgalactosamine
Original Article
Pathology
Sulfates
Sulfotransferase
Sulfotransferases - antagonists & inhibitors
Sulfotransferases - metabolism
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Summary:Chondroitin sulfate E (CS-E) plays a crucial role in diverse processes ranging from viral infection to neuroregeneration. Its regiospecific sulfation pattern, generated by N -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 IC 50 value ranging from 0.800 to 0.828 mM. They showed higher activities than benzyl D-GalNAc4S that was used as control.
ISSN:0282-0080
1573-4986
DOI:10.1007/s10719-018-9839-2