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1
Tetrafibricin, a novel non-peptide fibrinogen receptor antagonist, induces conformational changes in glycoprotein IIb/IIIa.替曲菲班，一种新型非肽类纤维蛋白原受体拮抗剂，可诱导糖蛋白IIb/IIIa发生构象变化。
Biochem J. 1994 Aug 1;301 ( Pt 3)(Pt 3):785-91. doi: 10.1042/bj3010785.
2
Tetrafibricin: a nonpeptidic fibrinogen receptor inhibitor from Streptomyces neyagawaensis (I). Its GPIIb/IIIa blockage on solid phase binding assay.四纤维蛋白溶菌素：一种来自根岸链霉菌的非肽类纤维蛋白原受体抑制剂（I）。其在固相结合试验中对糖蛋白IIb/IIIa的阻断作用。
Thromb Res. 1993 Dec 1;72(5):389-400. doi: 10.1016/0049-3848(93)90239-k.
3
The Arg-Gly-Asp (RGD) recognition site of platelet glycoprotein IIb-IIIa on nonactivated platelets is accessible to high-affinity macromolecules.在未活化血小板上，血小板糖蛋白IIb-IIIa的精氨酸-甘氨酸-天冬氨酸（RGD）识别位点可被高亲和力大分子识别。
Blood. 1992 May 1;79(9):2303-12.
4
Tetrafibricin: a nonpeptidic fibrinogen receptor inhibitor from Streptomyces neyagawaensis. (II). Its antiplatelet activities.四纤维蛋白溶菌素：一种来自根岸链霉菌的非肽类纤维蛋白原受体抑制剂。（II）。其抗血小板活性。
Thromb Res. 1993 Dec 1;72(5):401-12. doi: 10.1016/0049-3848(93)90240-o.
5
[Conformational changes of the platelet membrane glycoprotein IIb-IIIa complex stimulated by a monoclonal antibody to the N-terminal segment of glycoprotein IIIa].[抗糖蛋白IIIa N端片段单克隆抗体刺激下血小板膜糖蛋白IIb-IIIa复合物的构象变化]
Biokhimiia. 1996 Mar;61(3):412-28.
6
Tetrafibricin has a high selectivity for GPIIb/IIIa: comparison of the effects of tetrafibricin and RGDS on GPIIb/IIIa and the vitronectin receptor.替曲膦对糖蛋白IIb/IIIa具有高度选择性：替曲膦和RGDS对糖蛋白IIb/IIIa及玻连蛋白受体作用的比较。
Biochem Biophys Res Commun. 1994 Oct 14;204(1):325-32. doi: 10.1006/bbrc.1994.2463.
7
Reversible conformational changes induced in glycoprotein IIb-IIIa by a potent and selective peptidomimetic inhibitor.一种强效且选择性的拟肽抑制剂在糖蛋白IIb-IIIa中诱导的可逆构象变化。
Blood. 1992 Nov 15;80(10):2539-47.
8
Localization of the cross-linking sites of RGD and KQAGDV peptides to the isolated fibrinogen receptor, the human platelet integrin glycoprotein IIb/IIIa. Influence of peptide length.RGD和KQAGDV肽与分离的纤维蛋白原受体（人血小板整合素糖蛋白IIb/IIIa）交联位点的定位。肽长度的影响。
Eur J Biochem. 1992 Jun 15;206(3):759-65. doi: 10.1111/j.1432-1033.1992.tb16982.x.
9
Regulation of ligand binding to glycoprotein IIb-IIIa (integrin alpha IIb beta 3) in isolated platelet membranes.分离的血小板膜中配体与糖蛋白IIb-IIIa（整合素αIIbβ3）结合的调节。
Biochem J. 1993 Jun 15;292 ( Pt 3)(Pt 3):749-58. doi: 10.1042/bj2920749.
10
GPIIIa(90-102) and GPIIIa(631-653) epitopes as markers of conformational changes occurring during the activation of the glycoprotein IIb/IIIa complex.糖蛋白IIIa（90 - 102）和糖蛋白IIIa（631 - 653）表位作为糖蛋白IIb/IIIa复合物激活过程中发生构象变化的标志物。
Eur J Biochem. 1994 Sep 15;224(3):803-9. doi: 10.1111/j.1432-1033.1994.00803.x.

引用本文的文献

1
Asymmetric alcohol C-H allylation and syn-crotylation: C9-C20 of tetrafibricin.不对称醇 C-H 烯丙基化和顺式丙炔基化：四呋喃素的 C9-C20。
Org Lett. 2014 Feb 7;16(3):820-3. doi: 10.1021/ol403566w. Epub 2014 Jan 14.
2
Enantio- and diastereoselective synthesis of N-acetyl dihydrotetrafibricin methyl ester.对映选择性和非对映选择性合成 N-乙酰二氢四呋辛甲酯。
J Am Chem Soc. 2013 Apr 10;135(14):5340-3. doi: 10.1021/ja401918r. Epub 2013 Mar 26.
3
Development of a Double Allylboration Reagent Targeting 1,5-syn-(E)-Diols: Application to the Synthesis of the C(23)-C(40) Fragment of Tetrafibricin.一种用于合成1,5-顺式-(E)-二醇的双烯丙基硼化试剂的开发：应用于四纤维蛋白C(23)-C(40)片段的合成。
Tetrahedron. 2011 Sep 2;67(35):6497-6512. doi: 10.1016/j.tet.2011.06.008.
4
C(21)-C(40) of tetrafibricin via metal catalysis: beyond stoichiometric chiral reagents, auxiliaries, and premetalated nucleophiles.通过金属催化实现四肤菌素 C(21)-C(40)的构建：超越化学计量手性试剂、辅助试剂和预金属化亲核试剂。
Org Lett. 2011 May 6;13(9):2484-7. doi: 10.1021/ol200735r. Epub 2011 Apr 6.
5
Enantio- and diastereoselective synthesis of (E)-1,5-syn-diols: application to the synthesis of the C(23)-C(40) fragment of tetrafibricin.对映选择性和非对映选择性合成（E）-1,5-顺式二醇：在四纤维菌素 C(23)-C(40)片段合成中的应用。
Org Lett. 2011 Apr 1;13(7):1868-71. doi: 10.1021/ol2003836. Epub 2011 Mar 4.

本文引用的文献

1
Peptides derived from a sequence within beta 3 integrin bind to platelet alpha IIb beta 3 (GPIIb-IIIa) and inhibit ligand binding.源自β3整合素内序列的肽与血小板αIIbβ3（糖蛋白IIb-IIIa）结合并抑制配体结合。
J Biol Chem. 1993 Apr 5;268(10):6870-3.
2
Effects of heparin, aspirin and a synthetic platelet glycoprotein IIb-IIIa receptor antagonist (Ro 43-5054) on coronary artery reperfusion and reocclusion after thrombolysis with tissue-type plasminogen activator in the dog.肝素、阿司匹林及一种合成血小板糖蛋白IIb-IIIa受体拮抗剂（Ro 43-5054）对犬组织型纤溶酶原激活剂溶栓后冠状动脉再灌注及再闭塞的影响。
J Pharmacol Exp Ther. 1993 Jan;264(1):501-8.
3
MK-383 (L-700,462), a selective nonpeptide platelet glycoprotein IIb/IIIa antagonist, is active in man.MK-383（L-700,462）是一种选择性非肽类血小板糖蛋白IIb/IIIa拮抗剂，在人体中具有活性。
Circulation. 1993 Oct;88(4 Pt 1):1512-7. doi: 10.1161/01.cir.88.4.1512.
4
Tetrafibricin, a novel fibrinogen receptor antagonist. I. Taxonomy, fermentation, isolation, characterization and biological activities.四纤维蛋白溶菌素，一种新型纤维蛋白原受体拮抗剂。I. 分类、发酵、分离、特性及生物学活性。
J Antibiot (Tokyo). 1993 Jul;46(7):1039-46. doi: 10.7164/antibiotics.46.1039.
5
Tetrafibricin: a nonpeptidic fibrinogen receptor inhibitor from Streptomyces neyagawaensis. (II). Its antiplatelet activities.四纤维蛋白溶菌素：一种来自根岸链霉菌的非肽类纤维蛋白原受体抑制剂。（II）。其抗血小板活性。
Thromb Res. 1993 Dec 1;72(5):401-12. doi: 10.1016/0049-3848(93)90240-o.
6
Tetrafibricin: a nonpeptidic fibrinogen receptor inhibitor from Streptomyces neyagawaensis (I). Its GPIIb/IIIa blockage on solid phase binding assay.四纤维蛋白溶菌素：一种来自根岸链霉菌的非肽类纤维蛋白原受体抑制剂（I）。其在固相结合试验中对糖蛋白IIb/IIIa的阻断作用。
Thromb Res. 1993 Dec 1;72(5):389-400. doi: 10.1016/0049-3848(93)90239-k.
7
Clinical trials of platelet receptor inhibitors.血小板受体抑制剂的临床试验。
Thromb Haemost. 1993 Jul 1;70(1):94-8.
8
Ro 44-9883, a new nonpeptide glycoprotein IIb/IIIa antagonist, prevents platelet loss during experimental cardiopulmonary bypass.Ro 44-9883，一种新型非肽类糖蛋白IIb/IIIa拮抗剂，可防止实验性体外循环期间的血小板丢失。
J Thorac Cardiovasc Surg. 1993 Nov;106(5):834-41.
9
Regulation of ligand binding to glycoprotein IIb-IIIa (integrin alpha IIb beta 3) in isolated platelet membranes.分离的血小板膜中配体与糖蛋白IIb-IIIa（整合素αIIbβ3）结合的调节。
Biochem J. 1993 Jun 15;292 ( Pt 3)(Pt 3):749-58. doi: 10.1042/bj2920749.
10
Ligand intercellular adhesion molecule 1 has a necessary role in activation of integrin lymphocyte function-associated molecule 1.配体细胞间黏附分子1在整合素淋巴细胞功能相关分子1的激活中起必要作用。
Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5838-42. doi: 10.1073/pnas.90.12.5838.

替曲菲班，一种新型非肽类纤维蛋白原受体拮抗剂，可诱导糖蛋白IIb/IIIa发生构象变化。

Tetrafibricin, a novel non-peptide fibrinogen receptor antagonist, induces conformational changes in glycoprotein IIb/IIIa.

作者信息

Satoh T, Kouns W C, Yamashita Y, Kamiyama T, Steiner B

机构信息

Nippon Roche Research Center, Kanagawa, Japan.

出版信息

Biochem J. 1994 Aug 1;301 ( Pt 3)(Pt 3):785-91. doi: 10.1042/bj3010785.

DOI:10.1042/bj3010785
PMID:7519850
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1137056/
Abstract

Arg-Gly-Asp (RGD) is an amino acid sequence in fibrinogen recognized by platelet glycoprotein (GP) IIb/IIIa. Recently, it was found that RGD peptide binding to GPIIb/IIIa leads to conformational changes in the complex that are associated with the acquisition of high-affinity fibrinogen-binding function. In this study, we found that tetrafibricin, a novel non-peptidic GPIIb/IIIa antagonist, induced similar conformational changes in GPIIb/IIIa as did RGD peptides. Tetrafibricin increased the binding of purified inactive GPIIb/IIIa to immobilized pl-80, a monoclonal antibody that preferentially recognizes ligand-occupied GPIIb/IIIa. Exposure of the pl-80 epitope by tetrafibricin was also observed on resting human platelets by flow cytometry. On intact platelets, the conformational changes transformed GPIIb/IIIa into a high-affinity receptor for fibrinogen and triggered subsequent platelet aggregation. Tetrafibricin is the first non-peptidic GPIIb/IIIa antagonist reported that has the capacity to induce conformational changes in GPIIb/IIIa.

摘要

精氨酸-甘氨酸-天冬氨酸（RGD）是纤维蛋白原中的一段氨基酸序列，可被血小板糖蛋白（GP）IIb/IIIa识别。最近发现，RGD肽与GPIIb/IIIa结合会导致复合物的构象变化，这与获得高亲和力纤维蛋白原结合功能有关。在本研究中，我们发现新型非肽类GPIIb/IIIa拮抗剂替曲膦可诱导GPIIb/IIIa发生与RGD肽类似的构象变化。替曲膦增加了纯化的无活性GPIIb/IIIa与固定化pl-80（一种优先识别配体占据的GPIIb/IIIa的单克隆抗体）的结合。通过流式细胞术也观察到替曲膦在静息人血小板上暴露了pl-80表位。在完整血小板上，构象变化将GPIIb/IIIa转化为纤维蛋白原的高亲和力受体，并引发随后的血小板聚集。替曲膦是首个被报道具有诱导GPIIb/IIIa构象变化能力的非肽类GPIIb/IIIa拮抗剂。