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Glycoconjugate Journal

, Volume 35, Issue 5, pp 477–491 | Cite as

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

  • Seanghai Hor
  • Takumi Kodama
  • Nobuo Sugiura
  • Hikaru Kondou
  • Mio Yanagida
  • Keiya Yanagisawa
  • Aoki Shibasawa
  • Bunta Tsuzuki
  • Naoto Fukatsu
  • Kazuya Nagao
  • Kenji Yamana
  • Kazuya I. P. J. Hidari
  • Hideto Watanabe
  • Osami Habuchi
  • Hirofumi Nakano
Original Article
  • 167 Downloads

Abstract

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 IC50 value ranging from 0.800 to 0.828 mM. They showed higher activities than benzyl D-GalNAc4S that was used as control.

Keywords

Sulfotransferase N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase Inhibitor Chemical synthesis 

Abbreviations

CS-A

chondroitin sulfate A

CS-E

chondroitin sulfate E

GalNAc4S

2-acetamido-2-deoxy-4-O-sulfonato-D-galactopyranose

GalNAc4S-6ST

N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase

GalNAc4S6S

2-acetamido-2-deoxy-4,6-di-O-sulfonato-D-galactopyranose

GlcA

D-glucuronic acid

PAP

3′-phosphoadenosine 5′-phosphate

PAPS

3′-phosphoadenosine 5′-phosphosulfate

Notes

Funding

This work was supported by the Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University (to K.I.P.J.H, 2016-Ippan-11).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Seanghai Hor
    • 1
  • Takumi Kodama
    • 1
  • Nobuo Sugiura
    • 2
  • Hikaru Kondou
    • 1
  • Mio Yanagida
    • 1
  • Keiya Yanagisawa
    • 1
  • Aoki Shibasawa
    • 1
  • Bunta Tsuzuki
    • 1
  • Naoto Fukatsu
    • 1
  • Kazuya Nagao
    • 1
  • Kenji Yamana
    • 3
  • Kazuya I. P. J. Hidari
    • 4
  • Hideto Watanabe
    • 2
  • Osami Habuchi
    • 1
    • 5
  • Hirofumi Nakano
    • 1
  1. 1.Department of ChemistryAichi University of EducationKariyaJapan
  2. 2.Institute for Molecular Science of MedicineAichi Medical UniversityNagakuteJapan
  3. 3.Aichi Gakuin UniversityNisshinJapan
  4. 4.Junior College DivisionUniversity of AizuFukushimaJapan
  5. 5.Multidisciplinary Pain CenterAichi Medical UniversityNagakuteJapan

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