Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins

Tatsuki Koike; Aoi Sugimoto; Shuhei Kosono; Sumika Komaba; Yuko Kanno; Takashi Kitamura; Itsuki Anzai; Tokiko Watanabe; Daisuke Takahashi; Kazunobu Toshima

doi:10.1039/d1md00264c

Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins

Tatsuki Koike, Aoi Sugimoto, Shuhei Kosono, Sumika Komaba, Yuko Kanno, Takashi Kitamura, Itsuki Anzai, Tokiko Watanabe, Daisuke Takahashi, Kazunobu Toshima

Department of Applied Chemistry

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Fucoidan derivatives10-13, whose basic sugar chains are composed of repeating α(1,4)-linkedl-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure-activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that10exhibited the highest inhibitory activity of the fucoidan derivatives used. The inhibitory activity of10was much higher than that of fondaparinux, the reported ligand of SARS-CoV-2 S protein. Furthermore,10exhibited inhibitory activities against the binding of heparin with several mutant SARS-CoV-2 S proteins, but was found to not inhibit factor Xa (FXa) activity that could otherwise lead to undesirable anticoagulant activity.

Original language	English
Pages (from-to)	2016-2021
Number of pages	6
Journal	RSC Medicinal Chemistry
Volume	12
Issue number	12
DOIs	https://doi.org/10.1039/d1md00264c
Publication status	Published - 2021 Dec

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Organic Chemistry

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10.1039/d1md00264c

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title = "Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins",

abstract = "Fucoidan derivatives10-13, whose basic sugar chains are composed of repeating α(1,4)-linkedl-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure-activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that10exhibited the highest inhibitory activity of the fucoidan derivatives used. The inhibitory activity of10was much higher than that of fondaparinux, the reported ligand of SARS-CoV-2 S protein. Furthermore,10exhibited inhibitory activities against the binding of heparin with several mutant SARS-CoV-2 S proteins, but was found to not inhibit factor Xa (FXa) activity that could otherwise lead to undesirable anticoagulant activity.",

author = "Tatsuki Koike and Aoi Sugimoto and Shuhei Kosono and Sumika Komaba and Yuko Kanno and Takashi Kitamura and Itsuki Anzai and Tokiko Watanabe and Daisuke Takahashi and Kazunobu Toshima",

note = "Funding Information: This research was supported in part by JSPS KAKENHI Grant Number JP19H02724 in Scientific Research (B), JST CREST Grant Number JPMJCR20R3, and Keio Gijuku Academic Development Funds Funding Information: This research was supported in part by JSPS KAKENHI Grant Number JP19H02724 in Scientific Research (B), JST CREST Grant Number JPMJCR20R3, and Keio Gijuku Academic Development Funds. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry 2021.",

year = "2021",

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doi = "10.1039/d1md00264c",

language = "English",

volume = "12",

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T1 - Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins

AU - Koike, Tatsuki

AU - Sugimoto, Aoi

AU - Kosono, Shuhei

AU - Komaba, Sumika

AU - Kanno, Yuko

AU - Kitamura, Takashi

AU - Anzai, Itsuki

AU - Watanabe, Tokiko

AU - Takahashi, Daisuke

AU - Toshima, Kazunobu

N1 - Funding Information: This research was supported in part by JSPS KAKENHI Grant Number JP19H02724 in Scientific Research (B), JST CREST Grant Number JPMJCR20R3, and Keio Gijuku Academic Development Funds Funding Information: This research was supported in part by JSPS KAKENHI Grant Number JP19H02724 in Scientific Research (B), JST CREST Grant Number JPMJCR20R3, and Keio Gijuku Academic Development Funds. Publisher Copyright: © The Royal Society of Chemistry 2021.

PY - 2021/12

Y1 - 2021/12

N2 - Fucoidan derivatives10-13, whose basic sugar chains are composed of repeating α(1,4)-linkedl-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure-activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that10exhibited the highest inhibitory activity of the fucoidan derivatives used. The inhibitory activity of10was much higher than that of fondaparinux, the reported ligand of SARS-CoV-2 S protein. Furthermore,10exhibited inhibitory activities against the binding of heparin with several mutant SARS-CoV-2 S proteins, but was found to not inhibit factor Xa (FXa) activity that could otherwise lead to undesirable anticoagulant activity.

AB - Fucoidan derivatives10-13, whose basic sugar chains are composed of repeating α(1,4)-linkedl-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure-activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that10exhibited the highest inhibitory activity of the fucoidan derivatives used. The inhibitory activity of10was much higher than that of fondaparinux, the reported ligand of SARS-CoV-2 S protein. Furthermore,10exhibited inhibitory activities against the binding of heparin with several mutant SARS-CoV-2 S proteins, but was found to not inhibit factor Xa (FXa) activity that could otherwise lead to undesirable anticoagulant activity.

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Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins

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