biliverdin IX α | 2548-81-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四吡咯及其衍生物
• 英文名称: biliverdin IX α
• 英文别名: Biliverdin IXα；α-biliverdin；biliverdine；Biliverdin；BV
• CAS: 2548-81-4
• 化学式: C₃₃H₃₄N₄O₆
• 分子量: 582.656
• InChiKey: GWZYPXHJIZCRAJ-SRVCBVSDSA-N

物化性质

• 沸点：
  913.2±65.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.81
• 重原子数：
  43.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  160.95
• 氢给体数：
  5.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  胆红素 在 Haloferax volcanii US₀₂ laccase 、 sodium chloride 作用下， 以 aq. buffer 为溶剂， 生成 biliverdin IX α
  参考文献：
  名称：

  Haloferax volcanii laccase and variants and fragments thereof

  摘要：

  该发明涉及一种具有漆酶活性的新型纯化多肽以及编码该多肽的核酸序列。所公开的多肽在适度高温（从20°C以下到约70°C）、酸性和碱性pH条件、高盐浓度以及有机溶剂存在的情况下均能发挥作用。酶的高稳定性使其能够在甚至极端条件下广泛应用。该发明还提供了生产漆酶酶的方法。

  公开号：

  US08414660B2

文献信息

• Coupled Oxidation vs Heme Oxygenation:  Insights from Axial Ligand Mutants of Mitochondrial Cytochrome <i>b</i>₅
  作者：Ludivina Avila、Hong-wei Huang、Christopher O. Damaso、Shen Lu、Pierre Moënne-Loccoz、Mario Rivera

  DOI：10.1021/ja029311v

  日期：2003.4.1

  inhibit the oxidation of the heme in the H39V mutant is consistent with the formation of a coordinated hydroperoxide (Fe(III)(-)OOH), which in heme oxygenase is the precursor of meso-hydroxyheme. By comparison, mutation of His-63, the other axial ligand in OM cyt b(5), to Val results in a mutant (H63V) capable of oxidizing heme to verdoheme in the absence of catalase. However, the oxidation of heme by H63V

  将大鼠线粒体外膜细胞色素 b(5) (OM cyt b(5)) 中的轴向配体之一 His-39 突变为 Val 产生突变体 (H39V)，在孵育时能够将血红素氧化为胆绿素用肼和 O(2)。该反应通过形成含氧亚铁络合物 (Fe(II)(-)O(2)) 进行，该络合物被肼还原为氢过氧化铁 (Fe(III)(-)OOH) 物种。后者在卟啉上添加一个羟基以形成内消旋羟基血红素。过氧化氢酶不抑制 H39V 突变体中血红素氧化的观察结果与协调氢过氧化物 (Fe(III)(-)OOH) 的形成一致，其在血红素加氧酶中是中羟基血红素的前体。相比之下，OM cyt b(5) 中的另一个轴向配体 His-63 的突变，到 Val 导致突变体 (H63V) 能够在不存在过氧化氢酶的情况下将血红素氧化为绿素血红素。然而，H63V对血红素的氧化完全被过氧化氢酶抑制。此外，Fe(III)(-)H63V 与 H(2)O(2)
• [EN] PREPARATION METHOD FOR BILIVERDIN OR DERIVATIVE THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE LA BILIVERDINE OU DE SON DÉRIVÉ<br/>[ZH] 胆绿素或其衍生物的制备方法
  申请人：[en]POSEIDON PHARMACEUTICAL CO., LTD.;[zh]百顺药业有限公司

  公开号：WO2022134260A1

  公开（公告）日：2022-06-30

  一种胆绿素或其衍生物的制备方法，其由式2所示化合物制备得到，其中，式II表示单键或双键，A、B所示位置的式II分别独立地选自单键和双键中的一种，当式II表示单键时，与该单键相连的R1或R2选自对甲苯磺酰基，对甲苯亚磺酰基、苯磺酰基和苯亚磺酰基中的一种，当式II表示双键时，与该双键相连的R1或R2为氢。胆绿素或其衍生物的制备方法工艺简单，不需要柱层析方法，收率高，成本低，适合工业化生产；并且其减少了胆绿素二甲酯或胆绿素合成中产生的副产物，提高了产物纯度。
• [EN] BILIVERDIN COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF<br/>[FR] COMPOSÉ DE BILIVERDINE, ET SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 胆绿素类化合物及其制备方法和用途
  申请人：[en]POSEIDON PHARMACEUTICAL CO., LTD.;[zh]百顺药业有限公司

  公开号：WO2022134261A1

  公开（公告）日：2022-06-30

  一种胆绿素类化合物，其结构式如式1所示，其中，R选自氢、C1～C5烷基和苄基中的一种；式II表示双键或单键，A、B所示位置的式II分别独立地选自单键和双键中的一种，当式II为单键时，与该单键相连的R1或R2选自对甲苯砜基、对甲苯亚磺酰基、苯砜基、苯亚磺酰基；当式II为双键时，与该双键相连的R1或R2为氢。一种新的胆绿素或其类似物的中间体，其可以制备胆绿素或其类似物，制备工艺简单、高效、成本低、易于产业化；一种新的胆绿素或其类似物的中间体的制备方法，其制备工艺简单，条件温和，在室温下即可进行，成本低。
• Mechanism of Inactivation of Inducible Nitric Oxide Synthase by Amidines. Irreversible Enzyme Inactivation without Inactivator Modification
  作者：Yaoqiu Zhu、Dejan Nikolic、Richard B. Van Breemen、Richard B. Silverman

  DOI：10.1021/ja0445645

  日期：2005.1.1

  Nitric oxide synthases (NOS) are hemoproteins that catalyze the reaction Of L-arginine to L-Citrulline and nitric oxide. N-(3-(Aminomethyl)benzyl)acetamidine (1400W) was reported to be a slow, tight-binding, and highly selective inhibitor of iNOS in vitro and in vivo. Previous mechanistic studies reported that 1400W was recovered quantitatively after iNOS fully lost its activity and modification to iNOS was not detected. Here, it is shown that 1400W is a time-, concentration-, and NADPH-dependent irreversible inactivator of iNOS. HPLC-electrospray mass spectrometric analysis of the incubation mixture of iNOS with 1400W shows both loss of heme cofactor and formation of bilivedin, as was previously observed for iNOS inactivation by another amidine-containing compound, N-5(1-iminoethyl)-L-ornithine (L-NIO). The amount of biliverdin produced corresponds to the amount of heme lost by 1400W inactivation of iNOS. A convenient MS/MS-HPLC methodology was developed to identify the trace amount of biliverdin produced by inactivation of iNOS with either 1400W or L-NIO to be biliverdin \Xalpha out of the four possible regioisomers. Two mechanisms were previously proposed for iNOS inactivation by L-NIO: (1) uncoupling of the heme peroxide intermediate, leading to destruction of the heme to biliverdin; (2) abstraction of a hydrogen atom from the amidine methyl group followed by attachment to the heme cofactor, which causes the enzyme to catalyze the heme oxygenase reaction. The second mechanistic proposal was ruled out by inactivation of iNOS with d(3)-1400W, which produced no d(2)-1400W. Detection of carbon monoxide as one of the heme-degradation products further excludes the covalent heme adduct mechanism. On the basis of these results, a third mechanism is proposed in which the amidine inactivators of iNOS bind as does substrate L-arginine, but because of the amidine methyl group, the heme peroxy intermediate cannot be protonated, thereby preventing its conversion to the heme oxo intermediate. This leads to a change in the enzyme mechanism to one that resembles that of heme oxygenase, an enzyme known to convert heme to biliverdin \Xalpha.. This appears to be the first example of a compound that causes irreversible inactivation of an enzyme without itself becoming modified in any way.
• Oxidation of Heme to β- and δ-Biliverdin by <i>Pseudomonas a</i><i>eruginosa</i> Heme Oxygenase as a Consequence of an Unusual Seating of the Heme
  作者：Gregori A. Caignan、Rahul Deshmukh、Angela Wilks、Yuhong Zeng、Hong-wei Huang、Pierre Moënne-Loccoz、Richard A. Bunce、Margaret A. Eastman、Mario Rivera

  DOI：10.1021/ja0274960

  日期：2002.12.1

  The origin of the unusual regioselectivity of heme oxygenation, i.e. the oxidation of heme to delta-biliverdin (70%) and beta-biliverdin (30%), that is exhibited by heme oxygenase from Pseudomonas aeruginosa (pa-HO) has been studied by H-1 NMR, C-13 NMR, and resonance Raman spectroscopies. Whereas resonance Raman indicates that the heme-iron ligation in pa-HO is homologous to that observed in previously studied a-hydroxylating heme oxygenases, the NMR spectroscopic studies suggest that the heme in this enzyme is seated in a manner that is distinct from that observed for all other a-hydroxylating heme oxygenase enzymes for which a structure is known. In pa-HO, the heme is rotated in-plane similar to110degrees, so the delta-meso-carbon of the major orientational isomer is located within the HO-fold in the place where the a-hydroxylating enzymes typically place the alpha-meso-carbon. The unusual heme seating displayed by pa-HO places the heme propionates so that these groups point in the direction of the solvent-exposed heme edge and appears to originate in large part from the absence of stabilizing interactions between the polypeptide and the heme propionates, which are typically found in alpha-hydroxylating heme oxygenase enzymes. These interactions typically involve Lys-16 and Tyr-112, in Neisseriae meningitidis HO, and Lys-16 and Tyr-134, in human and rat HO-1. The corresponding residues in pa-HO are Asn-19 and Phe-117, respectively. In agreement with this hypothesis, we found that the Asn-19 Lys/Phe-117 Tyr double mutant of pa-HO exists as a mixture of molecules exhibiting two distinct heme seatings; one seating is identical to that exhibited by wild-type pa-HO, whereas the alternative seating is very similar to that typical of alpha-hydroxylating heme oxygenase enzymes and is related to the wild-type seating by similar to110degrees in-plane rotation of the heme. Furthermore, each of these heme seatings in the pa-HO double mutant gives rise to a subset of two heme isomeric orientations that are related to each other by 180degrees rotation about the alpha-gamma-meso-axis. The coexistence of these molecules in solution, in the proportions suggested by the corresponding area under the peaks in the H-1 NMR spectrum, explains the unusual regioselectivity of heme oxygenation observed with the double mutant, which we found produces alpha- (55%), delta- (35%), and beta-biliverdin (10%). a-Biliverdin is obtained by oxidation of the heme seated similar to that of a-hydroxylating enzymes, whereas beta- and delta-biliverdin are formed from the oxidation of heme seated as in wild-type pa-HO.