Abstract：
:Plasma hyaluronan-binding protein (PHBP), a serine protease that can activate coagulation factor VII and prourokinase, circulates in a single-chain form (pro-PHBP) and autoproteolytically converts to an active two-chain form with the aid of an effector such as spermidine and heparin. It has been postulated that PHBP plays roles in regulating inflammation, vascular function, fibrosis and atherosclerosis. From the comprehensive screening of natural sources for inhibitors of spermidine-induced pro-PHBP autoactivation, we identified several compounds with a polyphenol feature. Of these inhibitors, tannic acid (IC(50)=0.020 µM), delphinidin (IC(50)=0.079 µM), hamamelitannin (IC(50)=0.19 µM), (-)-epicatechin gallate (IC(50)=0.24 µM), and 3,5-di-O-caffeoylquinic acid (IC(50)=1.0 µM) were potent and selective, and did not inhibit heparin-induced pro-PHBP autoactivation and the active form of PHBP at concentrations 100 times higher than the respective IC(50) values. From evaluation of the activities of related compounds, it has been suggested that a compound with multiple aromatic rings with plural phenolic hydroxyl substituents exhibits potent activity. The inhibitory actions of delphinidin, hamamelitannin, (-)-epicatechin gallate and 3,5-di-O-caffeoylquinic acid were attenuated by catechol, a minimum polyphenol unit. Thus, it is likely that pro-PHBP binds these potent inhibitors through its site(s) that recognize a catechol-like structure. Our results would facilitate understanding of the molecular mechanism of pro-PHBP autoactivation and rational design of a compound for suppressing unregulated pro-PHBP activation.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Yamamoto E,Nishimura N,Okada K,Sekido C,Yamamichi S,Hasumi Kdoi
10.1248/bpb.34.462subject
Has Abstractpub_date
2011-01-01 00:00:00pages
462-70issue
4eissn
0918-6158issn
1347-5215pii
JST.JSTAGE/bpb/34.462journal_volume
34pub_type
杂志文章abstract：:By means of glycyrrhizin (GL)-affinity and Mono S column chromatographies (HPLC), at least four GL-binding proteins (p25, p17, p15-1 and p15-2) in the two Superdex fractions (P-II and P-III fractions) from Habu snake venom were selectively purified. By determination of their N-terminal partial amino acid sequences, a ...
journal_title：Biological & pharmaceutical bulletin
pub_type： 杂志文章
doi：10.1248/bpb.21.574
更新日期：1998-06-01 00:00:00
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doi：10.1248/bpb.27.1532
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pub_type： 杂志文章
doi：10.1248/bpb.18.1320
更新日期：1995-10-01 00:00:00
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doi：10.1248/bpb.20.243
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journal_title：Biological & pharmaceutical bulletin
pub_type： 杂志文章
doi：10.1248/bpb.17.756
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doi：10.1248/bpb.25.1562
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journal_title：Biological & pharmaceutical bulletin
pub_type： 杂志文章
doi：10.1248/bpb.23.283
更新日期：2000-03-01 00:00:00
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pub_type： 杂志文章
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pub_type： 临床试验,杂志文章
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更新日期：2001-07-01 00:00:00
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pub_type： 杂志文章
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更新日期：2007-06-01 00:00:00
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pub_type： 杂志文章
doi：10.1248/bpb.17.1018
更新日期：1994-08-01 00:00:00
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pub_type： 杂志文章
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更新日期：1999-07-01 00:00:00
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更新日期：2013-01-01 00:00:00
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更新日期：2019-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1248/bpb.27.528
更新日期：2004-04-01 00:00:00
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journal_title：Biological & pharmaceutical bulletin
pub_type： 杂志文章
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更新日期：2003-04-01 00:00:00
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更新日期：2020-01-01 00:00:00
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journal_title：Biological & pharmaceutical bulletin
pub_type： 杂志文章,评审
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更新日期：2013-01-01 00:00:00
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更新日期：2015-01-01 00:00:00
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更新日期：2005-01-01 00:00:00
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journal_title：Biological & pharmaceutical bulletin
pub_type： 杂志文章
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更新日期：2005-10-01 00:00:00
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journal_title：Biological & pharmaceutical bulletin
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更新日期：2008-01-01 00:00:00
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journal_title：Biological & pharmaceutical bulletin
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journal_title：Biological & pharmaceutical bulletin
pub_type： 杂志文章
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journal_title：Biological & pharmaceutical bulletin
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