N^ϖ-(7,8,9-trihydroxy-r-7,t-8,t-9,c-10-tetrahydobenzopyren-10-yl)histidine | 136616-43-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 英文名称: N^ϖ-(7,8,9-trihydroxy-r-7,t-8,t-9,c-10-tetrahydobenzopyren-10-yl)histidine
• 英文别名: N^ϖ-(7,8,9-trihydroxy-r-7,t-8,t-9,c-10-tetrahydobenzo[a]pyren-10-yl)histidine
• CAS: 136616-43-8
• 化学式: C₂₆H₂₃N₃O₅
• 分子量: 457.486
• InChiKey: WMNPKUIKOZISDW-PZXFSNNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  141.83
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  7,8-二羟基-9,10-环氧-7,8,9,10-四氢苯并[A]芘 、 L-组氨酸盐酸盐 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N^ϖ-(7,8,9-trihydroxy-r-7,t-8,t-9,c-10-tetrahydobenzopyren-10-yl)histidine 、 N^τ-(7,8,9-trihydroxy-r-7,t-8,t-9,c-10-tetrahydobenzopyren-10-yl)histidine
  参考文献：
  名称：

  Benzo[a]pyrene anti-diol epoxide covalently modifies human serum albumin carboxylate side chains and imidazole side chain of histidine(146)

  摘要：

  Human serum albumin was reacted with (+/-)-r-7,t-8-dihydroxy-t-9,t-10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BaPDE) in vitro and extracted to remove byproducts not covalently bound to the protein. Enzymatic digestion of the adducted protein in (HO)-H-2-O-18 at pH 8.2 and pH 10.0, followed by analysis of the released 7,8,9,10-tetrahydrotetrols by positive chemical ionization mass spectrometry for O-18 incorporation, revealed that carboxylic esters are formed by the epoxide. Analysis by HPLC/UV of the protein digest indicated that esters are the major product formed. Two additional stable products were also observed, accounting for 22 and 8% of chromatographed material. These were identical in UV absorption spectral characteristics with synthetic N(im)-histidine-anti-BaPDE adducts. Amino acid analysis of the peptide portion of the major product, in combination with its FAB mass spectrum, was consistent with a composition of histidine, proline, and tyrosine, while like analysis of the minor adducted peptide was consistent with a composition of histidine and proline. The first combination of amino acids occurs only once within the sequence of human albumin as His(146)-Pro(147)-Tyr(148). The second could be a subsequence of the first or correspond to His(338)-Pro(339) or His(440)-Pro(441). When synthetic His-Pro-Tyr was reacted with anti-BaPDE, a product which was chromatographically and spectrally (UV, FAB-MS) identical with the material isolated from alkylated albumin was formed in low yield. Reaction with fluorescamine followed by acid-catalyzed rearrangement of the products and analysis of the fluorescence spectra from the resulting materials revealed that the adducts in the protein resulted from alkylation of the imidazole tau-nitrogen of histidine. These results indicate that, in addition to the unknown amino acids esterified, His(146) and possibly His(338) or His(440), the former two of which are in a previously recognized binding site for certain covalent and noncovalent bulky aromatic ligands, are alkylated by anti-BaPDE to form enzymatically stable adducts.

  DOI：

  10.1021/ja00022a044