A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

Bang Claus G.; Jensen Jakob F.; Cohrt Emil OHanlon; Olsen Lasse B.; Siyum Saba G.; Mortensen Kim T.; Skovgaard Tine; Berthelsen Jens; Yang Liang; Givskov Michael; Qvortrup Katrine; Nielsen Thomas E.

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A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

机译：用于固相合成的异相合成的羟肟酸和HDAC6抑制剂的鉴定

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摘要

We herein present broadly useful, readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide hydroxamic acids. The inhibitory effects of the compounds were examined for seven HDAC enzyme subtypes using a chemiluminescence-based assay.

机译：我们在本文中为常规固相合成的常规实用，容易获得的和非羊羟胺接头。开发方案能够从各种树脂中有效合成和释放各种异羟肟酸，依赖于高控制和相对于试剂和合成方法的柔韧性。基于Trityl基羟胺接头合成肽异羟肟酸文库。使用基于化学发光的测定，检查化合物的抑制作用7 HDAC酶亚型。

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来源
《ACS combinatorial science》 |2017年第10期|共13页
作者
Bang Claus G.; Jensen Jakob F.; Cohrt Emil OHanlon; Olsen Lasse B.; Siyum Saba G.; Mortensen Kim T.; Skovgaard Tine; Berthelsen Jens; Yang Liang; Givskov Michael; Qvortrup Katrine; Nielsen Thomas E.;
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作者单位

Tech Univ Denmark Dept Chem DK-2800 Lyngby Denmark;

Tech Univ Denmark Dept Chem DK-2800 Lyngby Denmark;

Tech Univ Denmark Dept Chem DK-2800 Lyngby Denmark;

Tech Univ Denmark Dept Chem DK-2800 Lyngby Denmark;

Tech Univ Denmark Dept Chem DK-2800 Lyngby Denmark;

Tech Univ Denmark Dept Chem DK-2800 Lyngby Denmark;

Univ Copenhagen Dept Immunol &

Microbiol Costerton Biofilm Ctr DK-2200 Copenhagen Denmark;

Univ Copenhagen Dept Immunol &

Microbiol Costerton Biofilm Ctr DK-2200 Copenhagen Denmark;

Nanyang Technol Univ Singapore Ctr Environm Life Sci Engn Singapore 637551 Singapore;

Univ Copenhagen Dept Immunol &

Microbiol Costerton Biofilm Ctr DK-2200 Copenhagen Denmark;

Tech Univ Denmark Dept Chem DK-2800 Lyngby Denmark;

Tech Univ Denmark Dept Chem DK-2800 Lyngby Denmark;

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原文格式 PDF
正文语种 eng
中图分类化学;
关键词
solid phase synthesis; linker; hydroxamic acid; HDAC inhibitor;

机译：固相合成;接头;羟肟酸;HDAC抑制剂;

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专利

1. A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors [J] . Bang Claus G., Jensen Jakob F., Cohrt Emil OHanlon, ACS combinatorial science . 2017,第10期

机译：用于固相合成的异相合成的羟肟酸和HDAC6抑制剂的鉴定
2. N-linked hydroxylamine resin: Solid-phase synthesis of hydroxamic acids [J] . Yin Z, Low K, Lye P Synthetic Communications . 2005,第23期

机译：N-连接的羟胺树脂：异羟肟酸的固相合成
3. Toward an HDAC6 inhibitor: synthesis and conformational analysis of cyclic hexapeptide hydroxamic acid designed from α-tubulin sequence [J] . Binoy Jose, Shinji Okamura, Tamaki Kato, Bioorganic and medicinal chemistry . 2004,第6期

机译：针对HDAC6抑制剂：从α-微管蛋白序列设计的环六肽异羟肟酸的合成和构象分析
4. In silico modification of Zn~(2+) binding group of suberoylanilide hydroxamic acid (SAHA) by organoselenium compounds as Homo sapiens class II HDAC inhibitor of cervical cancer [C] . Usman Sumo Friend Tambunan, Ridla Bakri, Arli Aditya Parikesit Joint Conference on Chemisty . 2016

机译：通过有机烯化合物作为Zn〜（2+）结合基团的Zn〜（2+）结合基团的Zn〜（2+）结合基团的组织化合物作为宫颈癌的HOMO SAPIENS II HDAC抑制剂
5. 1. Matrix ESR study of radical cations of acyclic enedyne compounds. 2. A solid-phase synthesis and combinatorial approach to 2,3-dihydrobenzo[d]isothiazole 1,1-dioxide. 3. Synthesis of hyaluronic acid disaccharide and its c-linked analogue. [D] . Jiang, Bin. 1999

机译：1.无环烯炔化合物自由基阳离子的基质ESR研究。 2.2，3-二氢苯并[d]异噻唑1，1-二氧化物的固相合成和组合方法。 3.透明质酸二糖及其c-连接类似物的合成。
6. Metal-Free Direct Amidation of Naphthoquinones Using Hydroxamic Acids as Amides Source: Application in The Synthesis of A HDAC6 Inhibitor [O] . Cheng Zhang, C. James Chou -1

机译：异羟肟酸作为酰胺对萘醌的无金属直接酰胺化反应：在合成HDAC6抑制剂中的应用
7. A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors [O] . Bang Claus Gunnar, Jensen Jakob Feldthusen, Cohrt Anders Emil OHanlon, 2017

机译：用于固相合成异羟肟酸的连接子和HDaC6抑制剂的鉴定

A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

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