dimethyl 2,5-bis(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hexanedioate | 1109-18-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: dimethyl 2,5-bis(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hexanedioate
• 英文别名: 2,5-diphthalimido-adipic acid dimethyl ester；2,5-Diphthalimido-adipinsaeure-dimethylester；Dimethyl 2,5-bis(1,3-dioxoisoindol-2-yl)hexanedioate
• CAS: 1109-18-8
• 化学式: C₂₄H₂₀N₂O₈
• 分子量: 464.431
• InChiKey: WCLYVNPYCVTHFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  8

安全信息

• 海关编码：
  2925190090

反应信息

• 作为反应物：
  描述：

  dimethyl 2,5-bis(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hexanedioate 在 氢溴酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 336.0h， 以96%的产率得到2,5-二氨基己二酸
  参考文献：
  名称：

  Biomimetic Design Results in a Potent Allosteric Inhibitor of Dihydrodipicolinate Synthase from Campylobacter jejuni

  摘要：

  Dihydrodipicolinate synthase (DHDPS), an enzyme required for bacterial peptidoglycan biosynthesis, catalyzes the condensation of pyruvate and beta-aspartate semialdehyde (ASA) to form a cyclic product which dehydrates to form dihydrodipicolinate. DHDPS has, for several years, been considered a putative target for novel antibiotics. We have designed the first potent inhibitor of this enzyme by mimicking its natural allosteric regulation by lysine, and obtained a crystal structure of the protein inhibitor complex at 2.2 angstrom resolution. This novel inhibitor, which we named "bislysine", resembles two lysine molecules linked by an ethylene bridge between the alpha-carbon atoms. Bislysine is a mixed partial inhibitor with respect to the first substrate, pyruvate, and a noncompetitive partial inhibitor with respect to ASA, and binds to all forms of the enzyme with a K-i near 200 nM, more than 300 times more tightly than lysine. Hill plots show that the inhibition is cooperative, indicating that the allosteric sites are not independent despite being located on opposite sides of the protein tetramer, separated by approximately 50 angstrom. A mutant enzyme resistant to lysine inhibition, Y110F, is strongly inhibited by this novel inhibitor, suggesting this may be a promising strategy for antibiotic development.

  DOI：

  10.1021/jacs.5b12695
• 作为产物：
  描述：

  2,5-dibromoadipoyl dichloride 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 dimethyl 2,5-bis(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hexanedioate
  参考文献：
  名称：

  Biomimetic Design Results in a Potent Allosteric Inhibitor of Dihydrodipicolinate Synthase from Campylobacter jejuni

  摘要：

  Dihydrodipicolinate synthase (DHDPS), an enzyme required for bacterial peptidoglycan biosynthesis, catalyzes the condensation of pyruvate and beta-aspartate semialdehyde (ASA) to form a cyclic product which dehydrates to form dihydrodipicolinate. DHDPS has, for several years, been considered a putative target for novel antibiotics. We have designed the first potent inhibitor of this enzyme by mimicking its natural allosteric regulation by lysine, and obtained a crystal structure of the protein inhibitor complex at 2.2 angstrom resolution. This novel inhibitor, which we named "bislysine", resembles two lysine molecules linked by an ethylene bridge between the alpha-carbon atoms. Bislysine is a mixed partial inhibitor with respect to the first substrate, pyruvate, and a noncompetitive partial inhibitor with respect to ASA, and binds to all forms of the enzyme with a K-i near 200 nM, more than 300 times more tightly than lysine. Hill plots show that the inhibition is cooperative, indicating that the allosteric sites are not independent despite being located on opposite sides of the protein tetramer, separated by approximately 50 angstrom. A mutant enzyme resistant to lysine inhibition, Y110F, is strongly inhibited by this novel inhibitor, suggesting this may be a promising strategy for antibiotic development.

  DOI：

  10.1021/jacs.5b12695

文献信息

• Synthesis of stereoisomers of 2,4-diaminoglutaric and 2,5-diaminoadipic acids
  作者：V. P. Krasnov、E. A. Zhdanova、M. A. Korolyova、I. M. Bukrina、M. I. Kodess、V. Kh. Kravtsov、V. N. Biyushkin

  DOI：10.1007/bf02494371

  日期：1997.2

  Stereoisomers of 2,4-diaminoglutaric and 2,5-diaminoadipic acids were synthesized from glutamic and 2-aminoadipic acids, respectively. The stereochemistry of the products was established by IH NMR spectroscopy and X-ray analysis.
• An Improved Procedure for the Condensation of Potassium Phthalimide with Organic Halides
  作者：John C. Sheehan、William A. Bolhofer

  DOI：10.1021/ja01162a527

  日期：1950.6
• US3947445A
  申请人：——

  公开号：US3947445A

  公开（公告）日：1976-03-30
• US3951980A
  申请人：——

  公开号：US3951980A

  公开（公告）日：1976-04-20
• Biomimetic Design Results in a Potent Allosteric Inhibitor of Dihydrodipicolinate Synthase from <i>Campylobacter jejuni</i>
  作者：Yulia V. Skovpen、Cuylar J. T. Conly、David A. R. Sanders、David R. J. Palmer

  DOI：10.1021/jacs.5b12695

  日期：2016.2.17

  Dihydrodipicolinate synthase (DHDPS), an enzyme required for bacterial peptidoglycan biosynthesis, catalyzes the condensation of pyruvate and beta-aspartate semialdehyde (ASA) to form a cyclic product which dehydrates to form dihydrodipicolinate. DHDPS has, for several years, been considered a putative target for novel antibiotics. We have designed the first potent inhibitor of this enzyme by mimicking its natural allosteric regulation by lysine, and obtained a crystal structure of the protein inhibitor complex at 2.2 angstrom resolution. This novel inhibitor, which we named "bislysine", resembles two lysine molecules linked by an ethylene bridge between the alpha-carbon atoms. Bislysine is a mixed partial inhibitor with respect to the first substrate, pyruvate, and a noncompetitive partial inhibitor with respect to ASA, and binds to all forms of the enzyme with a K-i near 200 nM, more than 300 times more tightly than lysine. Hill plots show that the inhibition is cooperative, indicating that the allosteric sites are not independent despite being located on opposite sides of the protein tetramer, separated by approximately 50 angstrom. A mutant enzyme resistant to lysine inhibition, Y110F, is strongly inhibited by this novel inhibitor, suggesting this may be a promising strategy for antibiotic development.