amyloid β-protein fragment 25-35

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: amyloid β-protein fragment 25-35
• 英文别名: H2N-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-COOH；β-amyloid peptide residue 25-35 fragment；human β‐amyloid peptide 25 to 35；amyloid-β_25-35 peptide；β-amyloid protein fragment 25-35；amyloid β-peptide 25-35 fragment；L-Methionine,glycyl-L-seryl-L-asparaginyl-L-lysylglycyl-L-alanyl-L-isoleucyl-L-isoleucylglycyl-L-leucyl-；(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-[[2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]acetyl]amino]propanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoic acid
• 化学式: C₄₅H₈₁N₁₃O₁₄S
• 分子量: 1060.28
• InChiKey: WIHBNMPFWRHGDF-SLVFWPMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.9
• 重原子数：
  73
• 可旋转键数：
  37
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  469
• 氢给体数：
  15
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  、 amyloid β-protein fragment 25-35 以 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

  葡萄糖基铂 (II) 复合物抑制 Aβ 肽 C 末端区域的聚集

  摘要：

  神经退行性疾病通常是由不受控制的淀粉样蛋白聚集引起的。因此，许多药物发现过程都旨在评估能够调节自我识别机制的新化合物。在此，分析了两种相关的糖缀合物五配位 Pt(II) 复合物影响 β-淀粉样蛋白 C 末端区域的两个淀粉样蛋白生成片段 Aβ 21-40和 Aβ 25-35 的自聚集过程的能力（ Aβ）肽，阿尔茨海默病（AD）神经元斑块的主要成分。水溶性最强的复合物1Pt dep能够结合两个片段并深刻影响肽聚集体的形态。硫磺素 T (ThT) 结合测定、电喷雾电离质谱 (ESI-MS) 和紫外可见 (UV-vis) 吸收光谱表明1Pt dep对两个序列表现出不同的动力学和抑制机制，并证明肽聚集抑制作用与化合物金属中心与肽的直接配位键有关。这些数据支持五配位 Pt(II) 复合物在体外抑制淀粉样蛋白聚集体形成的能力，并为此类化合物作为潜在神经治疗药物的应用铺平了道路。

  DOI：

  10.1021/acs.inorgchem.1c03540
• 作为产物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-异亮氨酸 、 FMOC-赖氨酸 、 Fmoc-L-丝氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 amyloid β-protein fragment 25-35
  参考文献：
  名称：

  Solution Structure of Amyloid β-Peptide (25−35) in Different Media

  摘要：

  The design of molecules able to interact with the amyloid peptides either as inhibitors of fibril formation or as inhibitors of amyloid membrane pore formation represents one of the most relevant approaches in the development of anti-Alzheimer therapies. Abeta-(25-35), sequence GSNKGAIIGLM, is a highly toxic synthetic derivative of amyloid beta-peptides (Abeta-peptides), which forms fibrillary aggregates. Here, we report the NMR and CD investigation of Abeta-(25-35) in a membrane-mimicking environment and in isotropic mixtures of water and fluoro-alcohols to scan its conformational properties as a function of the medium. The analysis of the 3D structures in the mentioned conditions indicates a propensity of the peptide to behave as a typical transmembrane helix in the lipidic environment. In media characterized by different polarity, it loses the structural regularity at specific points of the sequence as a function of the environment. Furthermore, a comparison with the solution structure of full-length amyloid peptides suggests a role for the 25-27 kink region, which appears to be a general feature of all peptides under the solution conditions explored.

  DOI：

  10.1021/jm040773o

文献信息

• Piperazine and DBU: a safer alternative for rapid and efficient Fmoc deprotection in solid phase peptide synthesis
  作者：Krittika Ralhan、V. Guru KrishnaKumar、Sharad Gupta

  DOI：10.1039/c5ra23441g

  日期：——

  We demonstrate PolyAla synthesis using 5% piperazine + 2% DBU, which significantly reduces deletion products arising due to incomplete Fmoc-deprotection and can be used for deletion-free assembly of aggregation prone difficult peptides.

  我们使用5%哌嗪+2% DBU展示了PolyAla合成，这显著减少了由于Fmoc去保护不完全而产生的缺失产物，并可用于无缺失组装易聚集的难合成肽。
• Letter: β-Cyclodextrin Affects the Formation of Isomerization Products during Peptide Deamidation
  作者：Yulin Qi、Dietrich A. Volmer

  DOI：10.1255/ejms.1385

  日期：2015.8

  Cyclodextrins (CDs) are a group of nontoxic oligosaccharides that are widely used as drug excipients and protein stabilizers. CDs have also been found to reduce the neurotoxicity and fibrillation of amyloid beta (Aβ), the major component of the amyloid plaques found in the brain of patients suffering from Alzheimer's disease. The formation of these plaques was found to be enhanced by the presence of iso-aspartic acid (isoAsp) residues in the Aβ peptide, which can be formed by deamidation from asparagine (Asn). To explore further the influence of CDs on Aβ, we investigated three Asn-containing peptides, including Aβ25–35, by electrospray ionization, electron capture dissociation, and Fourier-transform ion cyclotron resonance mass spectrometry to explore details of the deamidation process in the presence and absence of peptide/CD adducts. The results showed that CDs reduced the formation of the isomerization product isoAsp during peptide deamidation. This finding might help to better understand the role of CDs during the protein-aggregation process.

  环糊精（CD）是一类无毒低聚糖，被广泛用作药物赋形剂和蛋白质稳定剂。研究还发现，环糊精能降低淀粉样 beta（Aβ）的神经毒性和纤维化，而淀粉样 beta 是阿尔茨海默病患者大脑中淀粉样斑块的主要成分。研究发现，Aβ肽中存在的异天冬氨酸（isoAsp）残基会促进这些斑块的形成，而天冬氨酸（Asn）可通过脱酰胺作用形成异天冬氨酸残基。为了进一步探究 CD 对 Aβ 的影响，我们采用电喷雾离子化、电子捕获解离和傅立叶变换离子回旋共振质谱法研究了 Aβ25-35 等三种含 Asn 的肽，以探究肽/CD 加合物存在和不存在时脱氨过程的细节。结果表明，CD 可减少肽脱酰胺过程中异构化产物 isoAsp 的形成。这一发现可能有助于更好地理解 CD 在蛋白质聚集过程中的作用。
• Synthesis of chemically-tethered amyloid-β segment trimer possessing amyloidogenic properties
  作者：Kiyomichi Shinoda、Youhei Sohma、Motomu Kanai

  DOI：10.1016/j.bmcl.2015.05.029

  日期：2015.8

  As amyloid-beta (A beta) undergoes dynamic aggregation, it is impossible to isolate ('hook') the transient A beta oligomer in an assembly state-pure form (e.g., sole A beta dimer, trimer, tetramer, etc.). Obtaining such a pure A beta oligomer would allow us to establish an in vitro system to perform a more detailed investigation of the pathogenic properties of the oligomer. A chemically-tethered A beta oligomer, constructed only by covalent bonds, could satisfy this demand. Here we designed a chemically-tethered trimer of a pathogenic A beta fragment (A beta(25-35)) (1) and successfully generated it in situ from its precursor (4), a water-soluble and nonaggregative O-acyl isopeptide of 1, in neutral aqueous media. Chemically-tethered 1 possessed stronger amyloidogenic properties, that is, potential for beta-sheet structure, fibril formation, and cytotoxicity, than the corresponding monomer A beta(25-35) (6). Trimerization of A beta(25-35) sequence might affect both the aggregative properties and cytotoxicity, based on the present results. This work opens the door for chemical synthesis of oligomers bigger than trimers in an assembly state-pure form, allowing for identification of the most toxic A beta oligomer. (C) 2015 Published by Elsevier Ltd.
• Solution Structure of Amyloid β-Peptide (25−35) in Different Media
  作者：Anna M. D'Ursi、Maria R. Armenante、Remo Guerrini、Severo Salvadori、Giuseppe Sorrentino、Delia Picone

  DOI：10.1021/jm040773o

  日期：2004.8.1

  The design of molecules able to interact with the amyloid peptides either as inhibitors of fibril formation or as inhibitors of amyloid membrane pore formation represents one of the most relevant approaches in the development of anti-Alzheimer therapies. Abeta-(25-35), sequence GSNKGAIIGLM, is a highly toxic synthetic derivative of amyloid beta-peptides (Abeta-peptides), which forms fibrillary aggregates. Here, we report the NMR and CD investigation of Abeta-(25-35) in a membrane-mimicking environment and in isotropic mixtures of water and fluoro-alcohols to scan its conformational properties as a function of the medium. The analysis of the 3D structures in the mentioned conditions indicates a propensity of the peptide to behave as a typical transmembrane helix in the lipidic environment. In media characterized by different polarity, it loses the structural regularity at specific points of the sequence as a function of the environment. Furthermore, a comparison with the solution structure of full-length amyloid peptides suggests a role for the 25-27 kink region, which appears to be a general feature of all peptides under the solution conditions explored.
• Glucosyl Platinum(II) Complexes Inhibit Aggregation of the C-Terminal Region of the Aβ Peptide
  作者：Sara La Manna、Marilisa Leone、Ilaria Iacobucci、Alfonso Annuziata、Concetta Di Natale、Elena Lagreca、Anna Maria Malfitano、Francesco Ruffo、Antonello Merlino、Maria Monti、Daniela Marasco

  DOI：10.1021/acs.inorgchem.1c03540

  日期：2022.2.28

  spectroscopy indicated that 1Ptdep shows different kinetics and mechanisms of inhibition toward the two sequences and demonstrated that the peptide aggregation inhibition is associated with a direct coordinative bond of the compound metal center to the peptides. These data support the in vitro ability of pentacoordinate Pt(II) complexes to inhibit the formation of amyloid aggregates and pave the way for the

  神经退行性疾病通常是由不受控制的淀粉样蛋白聚集引起的。因此，许多药物发现过程都旨在评估能够调节自我识别机制的新化合物。在此，分析了两种相关的糖缀合物五配位 Pt(II) 复合物影响 β-淀粉样蛋白 C 末端区域的两个淀粉样蛋白生成片段 Aβ 21-40和 Aβ 25-35 的自聚集过程的能力（ Aβ）肽，阿尔茨海默病（AD）神经元斑块的主要成分。水溶性最强的复合物1Pt dep能够结合两个片段并深刻影响肽聚集体的形态。硫磺素 T (ThT) 结合测定、电喷雾电离质谱 (ESI-MS) 和紫外可见 (UV-vis) 吸收光谱表明1Pt dep对两个序列表现出不同的动力学和抑制机制，并证明肽聚集抑制作用与化合物金属中心与肽的直接配位键有关。这些数据支持五配位 Pt(II) 复合物在体外抑制淀粉样蛋白聚集体形成的能力，并为此类化合物作为潜在神经治疗药物的应用铺平了道路。