bleomycin A₅ | 11116-32-8

• 物质功能分类: 原料药 - 抗肿瘤药 - 抗生素类抗肿瘤药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: bleomycin A₅
• 英文别名: pingyangmycin；bleomycin A5；bleomycin；BLM A5；Bleomycetin；[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5S,6S)-2-[(1R,2S)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[[(2R,3S,4S)-5-[[(2S,3R)-1-[2-[4-[4-[3-(4-aminobutylamino)propylcarbamoyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]ethylamino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-4-methyl-5-oxopentan-2-yl]amino]-1-(1H-imidazol-5-yl)-3-oxopropoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] carbamate
• CAS: 11116-32-8
• 化学式: C₅₇H₈₉N₁₉O₂₁S₂
• 分子量: 1440.58
• InChiKey: QYOAUOAXCQAEMW-UTXKDXHTSA-N

物化性质

• 密度：
  1.1028 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  -8.8
• 重原子数：
  99
• 可旋转键数：
  40
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  722
• 氢给体数：
  22
• 氢受体数：
  33

制备方法与用途

类别：有毒物质

毒性分级：中毒

急性毒性：

• 腹腔注射-大鼠 LD50: 102 毫克/公斤
• 口服-小鼠 LD50: 840 毫克/公斤

可燃性危险特性：热分解时排出有毒的氮氧化物和硫氧化物

储运特性：

• 库房需通风、低温且干燥保存

灭火剂：

• 水
• 干粉
• 干砂
• 二氧化碳
• 泡沫
• 1211 灭火剂

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5S,6S)-2-[(1R,2S)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[[(2R,3S,4S)-5-[[(2S,3R)-1-[2-[4-[4-[3-[4-[[(2S)-2-amino-3-methylbutanoyl]amino]butylamino]propylcarbamoyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]ethylamino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-4-methyl-5-oxopentan-2-yl]amino]-1-(1H-imidazol-5-yl)-3-oxopropoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] carbamate	——	C62H98N20O22S2	1539.71
  ——	[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5S,6S)-2-[(1R,2S)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[[(2R,3S,4S)-5-[[(2S,3R)-1-[2-[4-[4-[3-[4-[[(2R)-2-amino-3-methylbutanoyl]amino]butylamino]propylcarbamoyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]ethylamino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-4-methyl-5-oxopentan-2-yl]amino]-1-(1H-imidazol-5-yl)-3-oxopropoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] carbamate	——	C62H98N20O22S2	1539.71
  ——	[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5S,6S)-2-[(1R,2S)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[[(2R,3S,4S)-5-[[(2S,3R)-1-[2-[4-[4-[3-[4-[[(2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]butylamino]propylcarbamoyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]ethylamino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-4-methyl-5-oxopentan-2-yl]amino]-1-(1H-imidazol-5-yl)-3-oxopropoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] carbamate	——	C68H109N21O23S2	1652.87
  ——	[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5S,6S)-2-[(1R,2S)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[[(2R,3S,4S)-5-[[(2S,3R)-1-[2-[4-[4-[3-[4-[[(2S)-6-amino-2-[[(2S)-2-amino-3-methylbutanoyl]amino]hexanoyl]amino]butylamino]propylcarbamoyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]ethylamino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-4-methyl-5-oxopentan-2-yl]amino]-1-(1H-imidazol-5-yl)-3-oxopropoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] carbamate	——	C68H110N22O23S2	1667.89
  ——	[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5S,6S)-2-[(1R,2S)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[[(2R,3S,4S)-5-[[(2S,3R)-1-[2-[4-[4-[3-[4-[[(2S)-6-amino-2-[[(2R)-2-amino-3-methylbutanoyl]amino]hexanoyl]amino]butylamino]propylcarbamoyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]ethylamino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-4-methyl-5-oxopentan-2-yl]amino]-1-(1H-imidazol-5-yl)-3-oxopropoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] carbamate	——	C68H110N22O23S2	1667.89

反应信息

• 作为反应物：
  描述：

  (+)生物素-N-琥珀酰亚胺基酯 、 bleomycin A₅ 在 copper dichloride 、 乙二胺四乙酸 作用下， 以 水 为溶剂， 反应 48.0h， 以30%的产率得到biotinylated BLM A5
  参考文献：
  名称：

  [EN] CARBOHYDRATE-MEDIATED TUMOR TARGETING
  [FR] CIBLAGE DE TUMEURS MÉDIÉ PAR UN HYDRATE DE CARBONE

  摘要：

  本文提供的化合物可选择性地针对肿瘤，其中根据以下公式或其药用可接受的盐，其中RA和RB如本文所定义。肿瘤可通过本文描述的化合物进行成像或靶向治疗，其中至少一个RA或至少一个RB基团包含成像剂、治疗剂或特定结合对的成员，可与次级成像剂（如用于超声成像的微泡）结合。

  公开号：

  WO2011019419A1

文献信息

• [EN] COMPOUNDS AND MODULES FOR INHIBITION OF PRE-miR-21 AND THEIR USE IN TREATMENT OF CERTAIN CANCERS<br/>[FR] COMPOSÉS ET MODULES POUR INHIBER LE PRE-MIR-21 ET UTILISATIONS DE CEUX-CI DANS LE TRAITEMENT DE CERTAINS CANCERS
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2021087084A1

  公开（公告）日：2021-05-06

  Small molecule compounds and corresponding dimers having inhibitory activity against pre-miR-21 RNA and related methods for treatment of neoplastic disease such as cancer and especially cancers expressing miR-21 are disclosed.

  本发明涉及具有抑制pre-miR-21 RNA活性的小分子化合物以及相应的二聚体，以及用于治疗肿瘤性疾病，特别是表达miR-21的癌症的相关方法。
• Metallobleomycin-Mediated Cleavage of DNA Not Involving a Threading-Intercalation Mechanism
  作者：Anil T. Abraham、Xiang Zhou、Sidney M. Hecht

  DOI：10.1021/ja002460y

  日期：2001.6.1

  The DNA cleavage properties of metallobleomycins conjugated to three solid supports were investigated using plasmid DNA, relaxed covalently closed circular DNA, and linear duplex DNA as substrates. Cleavage of pBR322 and pSP64 plasmid DNAs by Fe(II).BLM A(5)-CPG-C(2) was observed with efficiencies not dissimilar to that obtained using free Fe(II).BLM A(5). Similar results were observed following Fe(II)

  使用质粒 DNA、松弛的共价闭合环状 DNA 和线性双链 DNA 作为底物研究了与三种固体支持物结合的金属博莱霉素的 DNA 切割特性。观察到 Fe(II).BLM A(5)-CPG-C(2) 对 pBR322 和 pSP64 质粒 DNA 的切割，其效率与使用游离 Fe(II).BLM A(5) 获得的效率并无不同。在 Fe(II).BLM A(5)-CPG-C(2) 介导的松弛质粒裂解后，观察到类似的结果，这是一种缺乏末端或负超螺旋的底物，能够促进链分离。BLM 共价连接到固体支持物，包括 Fe(II).BLM A(5)-Sepharose 4B、Fe(II).BLM A(5)-CPG-C(6) 和 Fe(II).BLM A(5) )-CPG-C(2)，以与游离 Fe(II).BLM A(5) 相同的序列选择性切割 5'-(32)P 末端标记的线性 DNA 双链体；解理主要在 5' -G(82)T(83)-3'
• A Short DNA Sequence Confers Strong Bleomycin Binding to Hairpin DNAs
  作者：Chenhong Tang、Ananya Paul、Mohammad P. Alam、Basab Roy、W. David Wilson、Sidney M. Hecht

  DOI：10.1021/ja505733u

  日期：2014.10.1

  assess sites of double-strand DNA cleavage. Both hairpin DNAs underwent double-strand cleavage at five sites within or near the original randomized eight base region. For DNA 12, four of the five double-strand cleavages involved independent single-strand cleavage reactions; DNA 13 underwent double-strand DNA cleavage by independent single-strand cleavages at all five sites. DNA 14, which bound Fe·BLM poorly

  博莱霉素 A5 和 B2 用于研究有助于 BLM-DNA 强相互作用的发夹 DNA 的结构特征。先前发现与这些 BLM 结合最紧密的 10 发夹 DNA 文库的两个成员随后被注意到共享序列 5'-ACGC（互补链序列 5'-GCGT）。每个都在 DNA 双链体的 8 个碱基对区域内或附近的五个位点进行双链切割，该区域已被随机化以创建原始文库。基于对固定化Fe(III)·BLM A5的亲和力选择了一个新的发夹DNA文库。30 个新鉴定的 DNA 中有两个也包含序列 5'-ACGC/5'-GCGT。这些 DNA 与 Fe(II)·BLM 的结合比以前表征的任何 DNA 都更紧密。表面等离子体共振证实了紧密的 Fe(III)·BLM B2 结合，并且非常适合 1:1 结合模型，暗示不存在重要的次级结合位点。Fe(II)·BLM A5 用于评估双链 DNA 切割位点。两个发夹 DNA 在原始随机八
• Carbohydrate Dependent Targeting of Cancer Cells by Bleomycin−Microbubble Conjugates
  作者：Jean-Charles Chapuis、Ryan M. Schmaltz、Krystal S. Tsosie、Marek Belohlavek、Sidney M. Hecht

  DOI：10.1021/ja8091104

  日期：2009.2.25

  Biotinylated bleomycin A(5) was attached to streptavidin-derivatized microbubbles, and a solution containing the conjugate was passed over a monolayer of cultured MCF-7 cells. The bleomycin-derivatized microbubbles adhered to the MCF-7 cells, and the association could be monitored by the use of a microscope. Three other cancer cell lines gave similar results. The bleomycin-microbubble conjugate did not bind to a normal breast cell tine (MCF-10A) or to the matched noncancer cell lines corresponding to the other cancer cell lines targeted by bleomycin. No binding to any tested cell tine was observed when the microbubbles; tacked conjugated bleomycin A(5) or when the microbubble contained a bleomycin A(5) analogue tacking the carbohydrate moiety.
• Novel peptide derivatives of bleomycin A5: Synthesis, antitumor activity and interaction with DNA
  作者：Zhi-Dong Xu、Min Wang、Su-Long Xiao、Ming Yang

  DOI：10.1016/j.bmcl.2005.06.021

  日期：2005.9

  A series of novel amino acid and peptide derivatives of bleomycin (BLM) A(5) were synthesized. All the compounds possessed significant antitumor activities in vitro against HL-60, BGC-823, PC-3MIE8, and MDA-MB-435 cell lines. Their antitumor activities against. MDA-MB-435 were 10-fold higher than BLM A(5). The DNA cleavage studies indicated that the hydrophobic amino acid or peptide derivatives of BLM A(5) could induce higher cleavage ratio of double to single strand DNA than BLM A(5). From the DNA binding studies, we found that the derivatives containing either D-conformation amino acid or basic amino acid could facilitate DNA binding of BLM. (c) 2005 Elsevier Ltd. All rights reserved.