H-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: H-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2
• 英文别名: (2S)-2-amino-N-[(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]pentanediamide
• 化学式: C₆₆H₁₀₅N₂₃O₁₆S
• 分子量: 1508.77
• InChiKey: NIARKDQHPVJRMK-SZRFEKISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.5
• 重原子数：
  106
• 可旋转键数：
  49
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  682
• 氢给体数：
  21
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  H-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 、 C₃₂H₂₈F₄FeN₂O₁₀^(1-) 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Monomeric and Dimeric ⁶⁸Ga-Labeled Bombesin Analogues for Positron Emission Tomography (PET) Imaging of Tumors Expressing Gastrin-Releasing Peptide Receptors (GRPrs)

  摘要：

  The GRPr, highly expressed in prostate PCa and breast cancer BCa, is a promising target for the development of new PET radiotracers. The chelator HBED-CC (N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) was coupled to the bombesin peptides: HBED-C-BN(2-14) 1, HBED-CC-PEG2-[D-Tyr(6),beta-Ala(11),Thi(13),Nle(14)]-BN(6-14) 2, HBED-CC-Y-[D-Phe(6),Sta(13),Leu(14)]-BN(6-14) (Y = 4-amino-1-carboxymethylpiperidine) 3, and HBED-CC-{PEG(2)-Y-[D-Phe(6),Sta(13),Leu(14)]-BN(6-14)}(2) 4 (homodimer). Compounds 1-4 presented high binding affinities for GRPr (T47D, 0.56-3.51 nM; PC-3, 2.12-4.68 nM). In PC-3 and T47D cells, agonists [Ga-68]1 and [Ga-68]2 were mainly internalized while antagonists [Ga-68]3 and [Ga-68]4 were surface bound. Cell-related radioactivity reached a maximum after 45 min, while tracer levels followed GRPr expression (PC-3 > T47D > LNCaP > MDA-MB-231). [Ga-68]4 showed the highest cell-bound radioactivity (PC-3 and T47D). In vivo, tumor (PC-3) targeting for [Ga-68]3 and [Ga-68]4 increased over time, with dynamic mu PET showing clearer tumors images at later time points. [Ga-68]3 and [Ga-68]4 can be considered suitable PET tracers for imaging PCa and BCa expressing GRPr.

  DOI：

  10.1021/acs.jmedchem.7b01856
• 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-蛋氨酸 、 Fmoc-N-三苯甲基-L-天冬酰胺 、 Fmoc-N-三苯甲基-L-谷氨酰胺 、 NΑ-FMOC-NΩ-(2,2,5,7,8-五甲基苯并二氢吡喃-6-磺酰基)-L-精氨酸 、 N-Fmoc-N'-三苯甲基-L-组氨酸 、 Fmoc-L-色氨酸(Boc)-OH 在 2-肟氰乙酸乙酯 、 N,N'-二异丙基碳二亚胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 H-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2
  参考文献：
  名称：

  A nucleus-directed bombesin derivative for targeted delivery of metallodrugs to cancer cells

  摘要：

  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.

  DOI：

  10.1016/j.jinorgbio.2020.111214