C6H5-SO2-Glu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 | 1155307-95-1

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: C6H5-SO2-Glu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2
• 英文别名: (4S)-5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-(benzenesulfonamido)-5-oxopentanoic acid
• CAS: 1155307-95-1
• 化学式: C₇₇H₁₁₆N₂₄O₂₁S₂
• 分子量: 1778.05
• InChiKey: UODRJRZHXTWMNB-XCYGWCKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  124
• 可旋转键数：
  58
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  774
• 氢给体数：
  24
• 氢受体数：
  25

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 C6H5-SO2-Glu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 在 human recombinant glutathione transferase isoenzyme GSTA₁-1 作用下， 生成 Bromobenzene-GSH conjugate
  参考文献：
  名称：

  Sulphonamide-based bombesin prodrug analogues for glutathione transferase, useful in targeted cancer chemotherapy

  摘要：

  Glutathione transferases (GSTs) are enzymes involved in cellular detoxification by catalysing the nucleophilic attack of glutathione (GSH) on the electrophilic centre of a number of toxic compounds and xenobiotics, including certain chemotherapeutic drugs. The encountered chemotherapeutic resistant of tumour cells, thus, has been associated with the increase of total GST expression. GSTs, in addition to GSH-conjugating activity, exhibit sulphonamidase activity, catalyzing the GSH-mediated hydrolysis of sulphonamide bonds. Such reactions are of interest as potential tumour-directed prodrug activation strategies. In the present work we report the design and synthesis of novel chimaeric sulphonamide derivatives of bombesin, able to be activated by the model human isoenzyme GSTA1-1 (hGSTA1-1). These derivatives bear a peptidyl-moiety (analogues of bombesin peptide: R-[Lue(13)]-bombesin, R-[Phe(13)]-bombesin and R-[Ser(3),Arg(10),Phe(13)]-bombesin, where R = C6H5SO2NH-) as molecular recognition element for targeting the drug selectively to turnout cells. The released S-alkyl-glutathione, after hGSTA1-1-mediated cleavage of the sulphonamide bond, provides an inhibitor of varied strength against GSTs from different sources. These prodrugs are envisaged as a plausible means to sensitize drug-resistant tumours that overexpress GSTs. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.10.009
• 作为产物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-缬氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-丙氨酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-O-叔丁基-L-谷氨酸 、 Fmoc-N-三苯甲基-L-天冬酰胺 、 Fmoc-N-三苯甲基-L-谷氨酰胺 、 N-Fmoc-N'-三苯甲基-L-组氨酸 、 Fmoc-L-色氨酸(Boc)-OH 、 Fmoc-Pbf-L-精氨酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 Rink amide MBHA resin 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 以79%的产率得到C6H5-SO2-Glu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2
  参考文献：
  名称：

  Sulphonamide-based bombesin prodrug analogues for glutathione transferase, useful in targeted cancer chemotherapy

  摘要：

  Glutathione transferases (GSTs) are enzymes involved in cellular detoxification by catalysing the nucleophilic attack of glutathione (GSH) on the electrophilic centre of a number of toxic compounds and xenobiotics, including certain chemotherapeutic drugs. The encountered chemotherapeutic resistant of tumour cells, thus, has been associated with the increase of total GST expression. GSTs, in addition to GSH-conjugating activity, exhibit sulphonamidase activity, catalyzing the GSH-mediated hydrolysis of sulphonamide bonds. Such reactions are of interest as potential tumour-directed prodrug activation strategies. In the present work we report the design and synthesis of novel chimaeric sulphonamide derivatives of bombesin, able to be activated by the model human isoenzyme GSTA1-1 (hGSTA1-1). These derivatives bear a peptidyl-moiety (analogues of bombesin peptide: R-[Lue(13)]-bombesin, R-[Phe(13)]-bombesin and R-[Ser(3),Arg(10),Phe(13)]-bombesin, where R = C6H5SO2NH-) as molecular recognition element for targeting the drug selectively to turnout cells. The released S-alkyl-glutathione, after hGSTA1-1-mediated cleavage of the sulphonamide bond, provides an inhibitor of varied strength against GSTs from different sources. These prodrugs are envisaged as a plausible means to sensitize drug-resistant tumours that overexpress GSTs. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.10.009

文献信息

• Sulphonamide-based bombesin prodrug analogues for glutathione transferase, useful in targeted cancer chemotherapy
  作者：I. Axarli、N.E. Labrou、C. Petrou、N. Rassias、P. Cordopatis、Y.D. Clonis

  DOI：10.1016/j.ejmech.2008.10.009

  日期：2009.5

  Glutathione transferases (GSTs) are enzymes involved in cellular detoxification by catalysing the nucleophilic attack of glutathione (GSH) on the electrophilic centre of a number of toxic compounds and xenobiotics, including certain chemotherapeutic drugs. The encountered chemotherapeutic resistant of tumour cells, thus, has been associated with the increase of total GST expression. GSTs, in addition to GSH-conjugating activity, exhibit sulphonamidase activity, catalyzing the GSH-mediated hydrolysis of sulphonamide bonds. Such reactions are of interest as potential tumour-directed prodrug activation strategies. In the present work we report the design and synthesis of novel chimaeric sulphonamide derivatives of bombesin, able to be activated by the model human isoenzyme GSTA1-1 (hGSTA1-1). These derivatives bear a peptidyl-moiety (analogues of bombesin peptide: R-[Lue(13)]-bombesin, R-[Phe(13)]-bombesin and R-[Ser(3),Arg(10),Phe(13)]-bombesin, where R = C6H5SO2NH-) as molecular recognition element for targeting the drug selectively to turnout cells. The released S-alkyl-glutathione, after hGSTA1-1-mediated cleavage of the sulphonamide bond, provides an inhibitor of varied strength against GSTs from different sources. These prodrugs are envisaged as a plausible means to sensitize drug-resistant tumours that overexpress GSTs. (C) 2008 Elsevier Masson SAS. All rights reserved.