bombesin

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: bombesin
• 英文别名: BBN；Pyr-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2；PGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2；(2S)-N-[(2S)-5-carbamimidamido-1-[(2S)-1-[2-[(2S)-1-[(2S)-1,5-dihydroxy-1-[(2S)-1-hydroxy-1-[(2S)-1-hydroxy-1-[(2S)-1-hydroxy-1-[2-hydroxy-2-[(2S)-1-hydroxy-1-[(2S)-1-hydroxy-1-[(2S)-1-hydroxy-1-imino-4-methylsulfanylbutan-2-yl]imino-4-methylpentan-2-yl]imino-3-(1H-imidazol-5-yl)propan-2-yl]iminoethyl]imino-3-methylbutan-2-yl]iminopropan-2-yl]imino-3-(1H-indol-3-yl)propan-2-yl]imino-5-iminopentan-2-yl]imino-1,4-dihydroxy-4-iminobutan-2-yl]imino-2-hydroxyethyl]imino-1-hydroxy-4-methylpentan-2-yl]imino-1-hydroxypentan-2-yl]-2-[[hydroxy-[(2S)-5-hydroxy-3,4-dihydro-2H-pyrrol-2-yl]methylidene]amino]pentanediimidic acid
• 化学式: C₇₁H₁₁₀N₂₄O₁₈S
• 分子量: 1619.87
• InChiKey: QXZBMSIDSOZZHK-DOPDSADYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.4
• 重原子数：
  114
• 可旋转键数：
  52
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  711
• 氢给体数：
  23
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  2-(4-(2-((2-carboxyphenyl)chloro-λ³-iodaneyl)-1,1,2,2-tetrafluoroethoxy)phenyl)-N-methylethan-1-aminium chloride 、 bombesin 在 sodium ascorbate 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  还原剂诱导的氮杂环和肽和蛋白质中固有的天然氨基酸残基的自由基氟代烷基化。

  摘要：

  制备了一系列氟代烷基化的环状λ3-碘化物及其盐酸盐，并与抗坏血酸钠在缓冲液或甲醇水溶液混合物中组合使用，以对一系列取代的吲哚，吡咯，色氨酸或其衍生物以及肽中的Trp残基进行自由基氟代烷基化。 。如在几种肽上所证明的，Trp，Tyr，Phe和His的芳香族氨基酸残基以对Trp的高选择性为目标。该功能化方法具有生物相容性，温和，快速且不含过渡金属。蛋白质肌红蛋白，泛素和人碳酸酐酶I也已成功功能化。

  DOI：

  10.1002/chem.201902944
• 作为产物：
  描述：

  蛙皮素九肽 、 bombesin
  参考文献：
  名称：

  KURANOVA, I. L.;CHURKINA, S. I.;LYUDMIROVA, V. L.;FILONOVA, E. B.;MUTULIS+, BIOORGAN. XIMIYA, 15,(1989) N, S. 748-762

  摘要：

  DOI：

文献信息

• Design, Synthesis, In Vitro, and Initial In Vivo Evaluation of Heterobivalent Peptidic Ligands Targeting Both NPY(Y1)- and GRP-Receptors—An Improvement for Breast Cancer Imaging?
  作者：Alicia Vall-Sagarra、Shanna Litau、Clemens Decristoforo、Björn Wängler、Ralf Schirrmacher、Gert Fricker、Carmen Wängler

  DOI：10.3390/ph11030065

  日期：——

  developed here such bispecific HBPLs and radiolabeled them with 68Ga, achieving high radiochemical yields, purities, and molar activities. We evaluated the HBPLs and their monospecific reference peptides in vitro regarding stability and uptake into different breast cancer cell lines and found that the 68Ga-HBPLs were efficiently taken up via the GRPR. We also performed in vivo PET/CT imaging and ex vivo biodistribution

  异二价肽配体（HBPL）设计用于独立处理两种不同的受体，是很有前途的肿瘤显像剂。例如，乳腺癌已显示出伴随并互补地过表达神经肽Y受体亚型1（NPY（Y1）R）和释放胃泌素的肽受体（GRPR）。因此，与单特异性配体相比，能够结合这两个受体的放射性标记的HBPL应该表现出更高的肿瘤靶向效率。我们在这里开发了这种双特异性HBPL，并用68Ga对其进行了放射性标记，从而实现了高放射化学产率，纯度和摩尔活性。我们评估了HBPL及其单特异性参考肽在体外的稳定性和对不同乳腺癌细胞系的吸收，并发现68Ga-HBPL通过GRPR被有效吸收。我们还对T-47D荷瘤小鼠进行了最有前途的68Ga-HBPL体内PET / CT成像和离体生物分布研究，并将结果与​​其加扰的类似物进行了比较。通过新开发的68Ga-HBPL可以很容易地看到肿瘤，并且与体内和体外的类似物相比，肿瘤的摄取和肿瘤与背景的比率都高得多。这些结果证
• Macrocyclic cyanine and indocyanine bioconjugates provide improved biomedical applications
  申请人：Achilefu Samuel

  公开号：US20070098638A1

  公开（公告）日：2007-05-03

  The sensitivity and specificity of the optical modality can be enhanced by the use of highly absorbing compounds as contrast agents. Novel macrocyclic cyanine and indocyanine bioconjugates that absorb and emit light in the near infrated region of electromagnetic spectrum are disclosed. These compounds are especially useful for endoscopic, localized photoacoustic, and sonofluorescence imaging, detection and therapy of tumors and other abnormalities.

  光学模式的灵敏度和特异性可以通过使用高度吸收的化合物作为对比剂来增强。本发明揭示了新型的大环氰染料和吲哚氰染料生物共轭物，它们在电磁谱的近红外区域吸收和发射光线。这些化合物特别适用于内窥镜、局部光声和声荧光成像、肿瘤和其他异常疾病的检测和治疗。
• MACROCYCLIC CYANINE AND INDOCYANINE BIOCONJUGATES PROVIDE IMPROVED BIOMEDICAL APPLICATION
  申请人：Achilefu Samuel

  公开号：US20110123450A1

  公开（公告）日：2011-05-26

  The sensitivity and specificity of the optical modality can be enhanced by the use of highly absorbing compounds as contrast agents. Novel macrocyclic cyanine and indocyanine bioconjugates that absorb and emit light in the near infrared region of electromagnetic spectrum are disclosed. These compounds are especially useful for endoscopic, localized photoacoustic, and sonofluorescence imaging, detection and therapy of tumors and other abnormalities.

  光学模式的灵敏度和特异性可以通过使用高度吸收的化合物作为对比剂来增强。本文介绍了一种新型的大环氰染料和吲哚氰染料生物共轭物，它们在电磁光谱的近红外区域吸收和发射光线。这些化合物特别适用于内窥镜、局部光声和声荧光成像、肿瘤和其他异常的检测和治疗。
• Diphenylphosphinylhydroxylamine (DPPH) Affords Late‐Stage S‐imination to access free‐NH Sulfilimines and Sulfoximines
  作者：Shanal Gunasekera、Alla Pryyma、Jimin Jung、Rebekah Greenwood、Brian O. Patrick、David M. Perrin

  DOI：10.1002/anie.202314906

  日期：2024.3.22

  O-(diphenylphosphinyl)hydroxyl amine to access sulfilimine salts and free-NH sulfoximines has been reported. Its generality was evidenced using a broad substrate scope along with late-stage functionalization of complex, biologically relevant substrates including a notorious amatoxin. DPPH was also shown to iminate sulfoxides with high yields under Rh catalysis to afford sulfoximines.

  已经报道了使用 O-(二苯基次膦基)羟基胺进行无金属、高产率的硫亚胺化以获得硫亚胺盐和游离 NH 亚磺酰亚胺。它的普遍性通过广泛的底物范围以及复杂的、生物学相关的底物（包括臭名昭著的鹅膏毒素）的后期功能化得到了证明。 DPPH 还被证明可以在 Rh 催化下以高产率亚胺化亚砜，得到亚砜亚胺。
• A nucleus-directed bombesin derivative for targeted delivery of metallodrugs to cancer cells
  作者：Sílvia Barrabés、Iteng Ng-Choi、María Ángeles Martínez、Blanca R. Manzano、Félix A. Jalón、Gustavo Espino、Lidia Feliu、Marta Planas、Rafael de Llorens、Anna Massaguer

  DOI：10.1016/j.jinorgbio.2020.111214

  日期：2020.11

  We have synthesized a set of bombesin derivatives with the aim of exploring their tumor targeting properties to deliver metal-based chemotherapeutics into cancer cells. Peptide QRLGNQWAVGHLL-NH₂ (BN3) was selected based on its high internalization in gastrin-releasing peptide receptor (GRPR)-overexpressing PC-3 cells. Three metallopeptides were prepared by incorporating the terpyridine Pt(II) complex [PtCl(cptpy)]Cl (1) (cptpy = 4'-(4-carboxyphenyl)-2,2':6,2″-terpyridine) at the N-terminus of BN3 or at the N^Ɛ- or N^α-amino group of an additional Lys residue (1-BN3, Lys-1-BN3 and 1-Lys-BN3, respectively). 1-Lys-BN3 displayed the best cytotoxic activity (IC₅₀: 19.2 ± 1.7 μM) and similar ability to intercalate into DNA than complex 1. Moreover, the polypyridine Ru(II) complex [Ru(bpy)₂)(cmbpy)](PF₆)₂ (2) (bpy = 2,2'-bipyridine; cmbpy = 4-methyl-2,2'-bipyridine-4'-carboxylic acid), with proven activity as photosensitizer, was coupled to BN3 leading to metallopeptide 2-Lys-BN3. Upon photoactivation, 2-Lys-BN3 displayed 2.5-fold higher cytotoxicity against PC-3 cells (IC₅₀: 7.6 ± 1.0 μM) than complex 2. To enhance the accumulation of the drugs into the cell nucleus, the nuclear localization signal (NLS) PKKKRKV was incorporated at the N-terminus of BN3. NLS-BN3 displayed higher cellular internalization along with nuclear biodistribution. Accordingly, metallopeptides 1-NLS-BN3 and 2-NLS-BN3 showed increased cytotoxicity (IC₅₀: 12.0 ± 1.1 μM and 2.3 ± 1.1 μM). Interestingly, the phototoxic index of 2-NLS-BN3 was 8-fold higher than that of complex 2. Next, the selectivity towards cancer cells was explored using 1BR3.G fibroblasts. Higher selectivity indexes were obtained for 1-NLS-BN3 and 2-NLS-BN3 than for the unconjugated complexes. These results prove NLS-BN3 effective for targeted delivery of metallodrugs to GRPR-overexpressing cells and for enhancing the cytotoxic efficacy of metal-based photosensitizers.