Peptidomimetics That Inhibit and Partially Reverse the Aggregation of A beta(1-42)

Stark Tina; Lieblein Tobias; Pohland Maximilian; Kalden Elisabeth; Freund Petra; Zangl Rene; Grewal Rekha; Heilemann Mike; Eckert Gunter P.; Morgner Nina; Goebel Michael W.

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Peptidomimetics That Inhibit and Partially Reverse the Aggregation of A beta(1-42)

机译：抑制和部分地逆转β（1-42）的聚集的肽微粒

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The peptide sequence KLVFF resembles the hydrophobic core of the A beta peptide known to form amyloid plaques in Alzheimer's disease. Starting from its retro-inverso peptide, we have synthesized three generations of peptidomimetics. Step by step natural amino acids have been replaced by aromatic building blocks accessible from the Pd-catalyzed Catellani reaction. The final compound 18 is stable against proteolytic decay and largely prevents the aggregation of A beta(1-42) overextended periods of time. The activity of the new inhibitors was tested first by fluorescence correlation spectroscopy. For closer examination of compound 18, additional techniques were also applied: laser-induced liquid bead ion desorption mass spectrometry, confocal laser scanning microscopy, thioflavin T fluorescence, and gel electrophoresis. Compound 18 not only retards the aggregation of chemically synthesized A beta but also can partially dissolve the oligomeric structures. Thioflavin binding mature fibrils, however, seem to resist the inhibitor.

机译：肽序列Klvff类似于已知在阿尔茨海默病中形成淀粉样斑块的β肽的疏水核心。从其复古逆肽开始，我们已经合成了三代肽模拟物。逐步逐步地通过从PD催化的Catellani反应中获得的芳族建筑物块代替。最终化合物18对蛋白水解衰减稳定，并且在很大程度上防止了β（1-42）过扩展时间的聚集。首先通过荧光相关光谱检测新抑制剂的活性。为了仔细检查化合物18，还施加了额外的技术：激光诱导的液体珠离子解吸质谱，共焦激光扫描显微镜，硫蛋白T荧光和凝胶电泳。化合物18不仅延迟了化学合成的β的聚集，而且可以部分地溶解低聚结构。然而，硫蛋白结合成熟的原纤维似乎抵抗抑制剂。

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《Biochemistry》 |2017年第36期|共10页
作者
Stark Tina; Lieblein Tobias; Pohland Maximilian; Kalden Elisabeth; Freund Petra; Zangl Rene; Grewal Rekha; Heilemann Mike; Eckert Gunter P.; Morgner Nina; Goebel Michael W.;
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作者单位

Goethe Univ Frankfurt Inst Organ Chem &

Chem Biol Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Goethe Univ Frankfurt Inst Phys &

Theoret Chem Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Goethe Univ Frankfurt Dept Pharmacol Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Goethe Univ Frankfurt Inst Organ Chem &

Chem Biol Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Goethe Univ Frankfurt Inst Phys &

Theoret Chem Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Goethe Univ Frankfurt Inst Phys &

Theoret Chem Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Justus Liebig Univ Giessen Inst Nutr Sci Wilhelmstr 20 D-35392 Giessen Germany;

Goethe Univ Frankfurt Inst Phys &

Theoret Chem Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Goethe Univ Frankfurt Dept Pharmacol Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Goethe Univ Frankfurt Inst Phys &

Theoret Chem Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

Goethe Univ Frankfurt Inst Organ Chem &

Chem Biol Campus Riedberg Max von Laue Str 7-9 D-60438 Frankfurt Germany;

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正文语种 eng
中图分类生物化学;
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1. Peptidomimetics That Inhibit and Partially Reverse the Aggregation of A beta(1-42) [J] . Stark Tina, Lieblein Tobias, Pohland Maximilian, Biochemistry . 2017,第36期

机译：抑制和部分地逆转β（1-42）的聚集的肽微粒
2. Kinetic and thermodynamic insights into the interaction of A beta 1-42 with astaxanthin and aggregation behavior of A beta 1-42: Surface plasmon resonance, microscopic, and molecular docking studies [J] . Dehghani Moharram, Jalal Razieh, Rashidi Mohammad-Reza Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena . 2021,第1期

机译：动力学和热力学洞察β1-42与脂肪素的相互作用和β1-42的聚集行为：表面等离子体共振，微观和分子对接研究
3. Ca2+ Interacts with Glu-22 of A beta(1-42) and Phospholipid Bilayers to Accelerate the A beta(1-42) Aggregation Below the Critical Micelle Concentration [J] . Yi Xinyao, Zhang Yi, Gong Ming, Biochemistry . 2015,第41期

机译：Ca2 +与Glu-22的A beta（1-42）和磷脂双层相互作用，以加速低于临界胶束浓度的A beta（1-42）聚集。
4. LILBID-MS REVEALS INFLUENCES OF THT AND COOMASSIE ON AGGREGATION KINETICS OF AMYLOID-BETA (1-42) AND α-SYNUCLEIN [C] . Janosch Martin, Rene Zangl, Tobias Lieblein, International Mass Spectrometry Conference . 2018

机译：LILBID-MS揭示了THT和COMASSIE对淀粉样蛋白β（1-42）和α-突触核蛋白的聚集动力学的影响
5. Protein aggregation studies: Inhibiting and encouraging beta-amyloid aggregation. [D] . Aucoin, Jed Paul. 2004

机译：蛋白质聚集研究：抑制和鼓励β淀粉样蛋白的聚集。
6. Comparing the Aggregation Free Energy Landscapes of Amyloid Beta(1-42) and Amyloid Beta(1-40) [O] . Weihua Zheng, Min-Yeh Tsai, Peter G. Wolynes -1

机译：比较淀粉样β（1-42）和淀粉样β（1-40）的聚集自由能态
7. Amyloid-beta peptide A beta p3-42 affects early aggregation of full-length A beta 1-42 [O] . Sanders, Hiromi M., Lust, Robert, Teller, Jan K. 2009

机译：淀粉样β肽A beta p3-42影响全长A beta 1-42的早期聚集

Peptidomimetics That Inhibit and Partially Reverse the Aggregation of A beta(1-42)

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