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

応用化学科

研究成果: Article › 査読

1 被引用数 (Scopus)

抄録

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.

本文言語	English
ページ（範囲）	2016-2021
ページ数	6
ジャーナル	RSC Medicinal Chemistry
巻	12
号	12
DOI	https://doi.org/10.1039/d1md00264c
出版ステータス	Published - 2021 12月

ASJC Scopus subject areas

生化学
分子医療
薬理学
薬科学
創薬
有機化学

文献へのアクセス

10.1039/d1md00264c

他のファイルとリンク

引用スタイル

Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins. / Koike, Tatsuki; Sugimoto, Aoi; Kosono, Shuhei; Komaba, Sumika; Kanno, Yuko; Kitamura, Takashi; Anzai, Itsuki; Watanabe, Tokiko; Takahashi, Daisuke ; Toshima, Kazunobu.

In: RSC Medicinal Chemistry, Vol. 12, No. 12, 12.2021, p. 2016-2021.

研究成果: Article › 査読

@article{c8d0013d21c746878cdc4e54d3c3919a,

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",

month = dec,

doi = "10.1039/d1md00264c",

language = "English",

volume = "12",

pages = "2016--2021",

journal = "RSC Medicinal Chemistry",

issn = "2040-2503",

publisher = "Royal Society of Chemistry",

number = "12",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=85121706822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85121706822&partnerID=8YFLogxK

U2 - 10.1039/d1md00264c

DO - 10.1039/d1md00264c

M3 - Article

AN - SCOPUS:85121706822

VL - 12

SP - 2016

EP - 2021

JO - RSC Medicinal Chemistry

JF - RSC Medicinal Chemistry

SN - 2040-2503

IS - 12

ER -

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

抄録

ASJC Scopus subject areas

文献へのアクセス

他のファイルとリンク

フィンガープリント

引用スタイル