Name: chemical inactivation of the e3 ubiquitin ligase cereblon by pomalidomide-based homo-protacs
Uploaded: 2019-05-15T14:00:00
Description: Watch this Scientific Journal Video about Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs at JoVE.com

这项工作得到了德国福森斯格明舍夫特(Emmy-Noether计划Kr-3886/2-1和SFB-1074到J.K.)的支持;FOR2372 到 M.G.)

1. PROTAC分子的制备
注意:使用前请查阅所有相关材料安全数据表 (MSDS)。这些合成中使用的几种化学品具有毒性和致癌性。请使用所有适当的安全操作和个人防护设备。
<ol><li>制备三丁基N-(2,6-二恶英-3-烟酸)碳水化合物(化合物1)
	<ol>
<li>在带搅拌棒并配有反流冷凝器的100 mL圆形底瓶中,在100 mL圆形瓶中加入1,1'-碳二甲酰胺(1.95克,12毫摩尔)和4-(二甲基氨基)...

<ol>
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E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phthalimide+conjugation+as+a+strategy+for+in+vivo+target+protein+degradation.">Phthalimide conjugation as a strategy for in vivo target protein degradation.</a> Science. 348 (6241), 1376-1381 (2015).</li><li>Maniaci, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Homo-PROTACs:+bivalent+small-molecule+dimerizers+of+the+VHL+E3+ubiquitin+ligase+to+induce+self-degradation.">Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation.</a> Nature Communications. 8 (1), 830 (2017).</li><li>Crew, A. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+and+Characterization+of+Von+Hippel-Lindau-Recruiting+Proteolysis+Targeting+Chimeras+(PROTACs)+of+TANK-Binding+Kinase+1.">Identification and Characterization of Von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1.</a> Journal of Medicinal Chemistry. , (2017).</li><li>Lu, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hijacking+the+E3+Ubiquitin+Ligase+Cereblon+to+Efficiently+Target+BRD4.">Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4.</a> Chemistry &amp; Biology. 22 (6), 755-763 (2015).</li><li>Steinebach, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PROTAC-mediated+crosstalk+between+E3+ligases.">PROTAC-mediated crosstalk between E3 ligases.</a> Chemical Communications. 55 (12), 1821-1824 (2019).</li><li>Tinworth, C. 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X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cereblon+expression+is+required+for+the+antimyeloma+activity+of+lenalidomide+and+pomalidomide.">Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide.</a> Blood. 118 (18), 4771-4779 (2011).</li><li>Kortum, K. 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此处描述的CRBN此类同质-PROTAC的设计依赖于波马利多米德与CRBN的具体亲和力,该设计已成功应用于众多异质功能PROTAC,并使得PROTAC 8的发展成为高度选择性CRBN降解剂。我们的分子的特异性已经通过蛋白体分析24得到证实。对于基因介导的淘汰,排除和验证副作用是具有挑战性的和耗时的。此外,化学诱导的敲除是可逆的,快速和直接适用于广泛的细胞和组织类?...

免疫调节药物 (IMiDs) 沙利度胺及其类似物, 利利多米德和波马利多米德, 所有批准用于治疗多发性骨髓瘤, 结合 E3 泛素结合脑素 (CRBN), 基质适配器的 cullinin4A-RING E3 泛素结合(CRL4CRBN)1,2,3.IMiD 的结合增强了 CRL4CRBN与淋巴转录因子 Ikaros (IKZF1) 和 Aiolos (IKZF3) 的亲和力,导致其泛化和降解(图 1)4,5 ,6,7,8. 由于 IKZF1 和 IKZF3 对多发性骨髓瘤细胞至关重要,因此它们的失活会导致生长抑制。SALL4最近被发现作为CRBN的另一种IMiD诱导的新基质,可能是导致致畸和所谓的康特甘灾难在1950年代由沙利多米德9,10造成的。相反,卡辛激酶1+(CK1+)是CRBN的一种利利多米德特异性基质,与染色体5q缺失11的骨髓增生综合征的治疗效果有关。
小分子靶向特定蛋白质降解的能力是现代药物开发中令人振奋的一个暗示。虽然沙利度胺及其类似物的机制是在人类首次使用后发现的,但所谓的Proteolyis Targeting Chimeras (PROTACs) 被设计为专门针对感兴趣的蛋白质 (POI)(图2)12,13,14,15,16,17,18。PROTACs 是异体功能分子,由 POI 的特定配体组成,通过链接器连接到 E3 泛性联苯的配体,如 CRBN 或 von-Hippel-Lindau (VHL)18、19、20、 21,22.PROTACs诱导形成瞬态三元复合物,将POI定向到E3泛基质连体酶,导致其泛化和蛋白酶降解。与常规抑制剂相比,PROTACs的主要优点是,与POI结合就足够了,而不是其抑制作用,因此PROTACs可能针对更广泛的蛋白质,包括那些被认为无法药物的蛋白质,转录因子15.此外,嵌合分子具有催化作用,因此具有高效力。在泛基辛转移到POI后,三元复合物分离,可用于形成新的复合物。因此,非常低的PROTAC浓度足以降解靶蛋白23。
在这里,我们描述了一个波马利多米德-波马利多米德共聚物(化合物8)的合成,它招募CRBN来降低自身24。E3 泛基苯甲二苯CRBN 同时充当招募者和目标(图 3)。为了验证我们的数据,我们还合成了负绑定控制(化合物9)。 我们的数据证实,新合成的同质性PROTAC是CRBN降解的特异性,对其他蛋白质的影响最小。

<table>
	<tbody>
		<tr>
			<td>1,1&#39;-Carbonyldiimidazole</td>
			<td>TCI chemicals</td>
			<td>C0119</td>
			<td></td>
		</tr>
		<tr>
			<td>2,2&#8242;-(Ethylenedioxy)-bis(ethylamine)</td>
			<td>Sigma-Aldrich</td>
			<td>385506</td>
			<td>Compound 6</td>
		</tr>
		<tr>
			<td>2-Mercaptoethanol</td>
			<td>Sigma-Aldrich</td>
			<td>M6250</td>
			<td></td>
		</tr>
		<tr>
			<td>3-Fluorophthalic anhydride, 98 %</td>
			<td>Alfa Aesar</td>
			<td>A12275</td>
			<td></td>
		</tr>
		<tr>
			<td>4-Dimethylaminopyridine, 99 %</td>
			<td>Acros</td>
			<td>148270250</td>
			<td>Toxic</td>
		</tr>
		<tr>
			<td>Acrylamidstamml&#246;sung/ Bisacrylamid (30%/0,8%)</td>
			<td>Carl Roth</td>
			<td>3029.1</td>
			<td></td>
		</tr>
		<tr>
			<td>Aiolos (D1C1E) mAB</td>
			<td>Cell signaling</td>
			<td>15103S</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-CRBN antibody produced in rabbit</td>
			<td>Sigma</td>
			<td>HPA045910</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-rabbit IgG HRP-linked antibody</td>
			<td>Sigma</td>
			<td>7074S</td>
			<td></td>
		</tr>
		<tr>
			<td>Ammonium Persulfate</td>
			<td>Roth</td>
			<td>9592.2</td>
			<td></td>
		</tr>
		<tr>
			<td>Boc-Gln-OH</td>
			<td>TCI chemicals</td>
			<td>B1649</td>
			<td></td>
		</tr>
		<tr>
			<td>Bovine Serum Albumin</td>
			<td>Sigma-Aldrich</td>
			<td>A7906-100G</td>
			<td></td>
		</tr>
		<tr>
			<td>CellTiter-Glo Luminescent Cell Viability Assay</td>
			<td>Promega</td>
			<td>G7571</td>
			<td></td>
		</tr>
		<tr>
			<td>ChemiDoc XRS+</td>
			<td>Bio-Rad</td>
			<td>1708265</td>
			<td></td>
		</tr>
		<tr>
			<td>DMF, anhydrous, 99.8 %</td>
			<td>Acros</td>
			<td>348435000</td>
			<td>Extra Dry over Molecular Sieve</td>
		</tr>
		<tr>
			<td>DMSO, anhydrous, 99.7 %</td>
			<td>Acros</td>
			<td>348445000</td>
			<td>Extra Dry over Molecular Sieve</td>
		</tr>
		<tr>
			<td>Glycine</td>
			<td>Sigma-Aldrich</td>
			<td>15523-1L-R</td>
			<td></td>
		</tr>
		<tr>
			<td>Goat anti-mouse (HRP conjugated)</td>
			<td>Santa Cruz biotechnology</td>
			<td>sc-2005</td>
			<td></td>
		</tr>
		<tr>
			<td>Halt Protease &#38; Phosphatase Inhibitor Single-use Cocktail (100X)</td>
			<td>Thermo Scientific</td>
			<td>1861280</td>
			<td></td>
		</tr>
		<tr>
			<td>Ikaros (D6N9Y) Mab</td>
			<td>Cell signaling</td>
			<td>14859S</td>
			<td></td>
		</tr>
		<tr>
			<td>ImmobilonP Transfer Membrane (0,45&#181;m)</td>
			<td>Merck</td>
			<td>IPVH000010</td>
			<td></td>
		</tr>
		<tr>
			<td>Iodomethane, 99 %</td>
			<td>Sigma-Aldrich</td>
			<td>I8507</td>
			<td>Highly toxic</td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>Sigma-Aldrich</td>
			<td>32213-2.5L</td>
			<td></td>
		</tr>
		<tr>
			<td>Mg132</td>
			<td>Selleckchem</td>
			<td>S2619</td>
			<td></td>
		</tr>
		<tr>
			<td>Mini Trans-Blot electrophoretic transfer cell</td>
			<td>Bio-Rad</td>
			<td>1703930</td>
			<td></td>
		</tr>
		<tr>
			<td>Mini-PROTEAN Tetra Vertical Electrophoresis Cell</td>
			<td>Bio-Rad</td>
			<td>1658004</td>
			<td></td>
		</tr>
		<tr>
			<td>MLN4942</td>
			<td>biomol (cayman)</td>
			<td>Cay15217-1</td>
			<td></td>
		</tr>
		<tr>
			<td>Monoclonal Anti-&#945;-Tubulin antibody produced in mouse (B512)</td>
			<td>Sigma</td>
			<td>T5168</td>
			<td></td>
		</tr>
		<tr>
			<td>N-Ethyldiisopropylamine, 99 %</td>
			<td>Alfa Aesar</td>
			<td>A11801</td>
			<td></td>
		</tr>
		<tr>
			<td>Nonfat dried milk powder</td>
			<td>PanReac AppliChem</td>
			<td>A0830,0500</td>
			<td></td>
		</tr>
		<tr>
			<td>Nunc F96 MicroWell White Polystyrene Plate</td>
			<td>Thermo Scientific</td>
			<td>136101</td>
			<td></td>
		</tr>
		<tr>
			<td>NuPAGE LDS Sample Buffer (4X)</td>
			<td>Thermo Scientific</td>
			<td>NP0008</td>
			<td></td>
		</tr>
		<tr>
			<td>Pierce BCA Protein Assay kit</td>
			<td>Thermo Scientific</td>
			<td>23225</td>
			<td></td>
		</tr>
		<tr>
			<td>Pomalidomide</td>
			<td>Selleckchem</td>
			<td>S1567</td>
			<td></td>
		</tr>
		<tr>
			<td>RestoreTM Western Blot Stripping Buffer</td>
			<td>Thermo Scientific</td>
			<td>46430</td>
			<td></td>
		</tr>
		<tr>
			<td>sodium dodecyl sulfate</td>
			<td>Carl Roth</td>
			<td>183.1</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium Chloride</td>
			<td>Sigma-Aldrich</td>
			<td>A9539-500g</td>
			<td></td>
		</tr>
		<tr>
			<td>TEMED</td>
			<td>Carl Roth</td>
			<td>2367.3</td>
			<td></td>
		</tr>
		<tr>
			<td>tert-Butyl N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]carbamate</td>
			<td>Sigma-Aldrich</td>
			<td>89761</td>
			<td>Compound 5</td>
		</tr>
		<tr>
			<td>Tricin</td>
			<td>Carl Roth</td>
			<td>6977.4</td>
			<td></td>
		</tr>
		<tr>
			<td>Trizma base</td>
			<td>Sigma-Aldrich</td>
			<td>T1503-1kg</td>
			<td></td>
		</tr>
		<tr>
			<td>Tween-20</td>
			<td>Sigma-Aldrich</td>
			<td>P7949-500ml</td>
			<td></td>
		</tr>
		<tr>
			<td>WesternBright ECL spray</td>
			<td>Advansta</td>
			<td>K-12049-D50</td>
			<td></td>
		</tr>
	</tbody>
</table>

chemical inactivation of the e3 ubiquitin ligase cereblon by pomalidomide-based homo-protacs

免疫调节药物 (IMiDs) 沙利度胺及其类似物, 利利多米德和波马利多米德, 所有FDA批准的药物用于治疗多发性骨髓瘤, 诱导淋巴转录因子伊卡罗斯 (IKZF1) 和 Aiolos 的泛化和降解(IKZF3)通过脑蛋白酶(CRBN)E3泛蛋白联苯,用于蛋白酶降解。IMiDs最近被用于生成双功能蛋白解靶向嵌合物(PROTACs),以针对CRBN E3附和酶的泛化和蛋白酶降解的其他蛋白质。我们设计并合成了基于波马利多米德的同质功能PROTC,并分析了它们诱导CRBN自导无化和降解的能力。在这里,CRBN同时充当E3泛基丁和靶子。同质-PROTAC化合物8降解CRBN具有高效力,对IKZF1和IKZF3仅产生最小剩余影响。化合物8的CRBN失活对细胞活力和不同多发性骨髓瘤细胞系的增殖没有影响。这种同质性PROTAC可以废除多发性骨髓瘤细胞中IMiD的作用。因此,我们的同质性波马利多米德化合物可能有助于识别CRBN的内源基质和生理功能,并研究IMiD的分子机制。

在这里,我们描述了基于同质的波马利多米德PROTAC用于CRBN降解的设计、合成和生物评价。我们的PROTAC与两个CRBN分子同时相互作用,形成三元复合物,诱导CRBN自泛化和原体降解,仅对波马利多米德诱导的新基质IKZF1或IKZF3产生最小剩余影响。
在以前公布的一系列基于波马利多米德的PROTAC分子24中,化合物8...

Watch this Scientific Journal Video about Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs at JoVE.com

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

这项工作描述了一种基于波马利多米德的合成和表征,即一种基于双功能的同质性PROTAC,作为诱导E3泛性联苯基雷布龙(CRBN)的泛化和降解的新方法,该物质是沙利度胺类比靶的目标。

以波马利多米德为基础的人种-PROTACs对E3泛基金的化学灭活

The immunomodulatory drugs (IMiDs) thalidomide and its analogs, lenalidomide and pomalidomide, all FDA approved drugs for the treatment of multiple ...

我们的同质PROTACs是Cereblon的第一个化学抑制剂，可能有助于进一步阐明沙利度胺类比的分子机制，以及研究Cereblon的生理功能。这种新的 PROTAC 平台技术对于专门针对那些被认为无法追踪的感兴趣的蛋白质非常有用。CRBN抑制本身没有抗肿瘤活性。然而，CRBN降解器可能对肥胖、传染病和其他疾病有临床影响。合成具有挑战性，在设计 PROTAC 化合物时，很难找到最佳的链接剂和附件来生成有效的蛋白质降解剂。首先，将 2.46 克受 Boc 保护的 L-谷氨酰胺和 50 毫升四氢素放在 100 毫升圆底烧瓶中，并在 800 rpm 转速下搅拌一分钟。然后，加入1.95克1，1'碳二米达佐和催化量4-丙胺。在回流下继续搅拌 10 小时，以获得谷氨酸化合物的透明无色溶液。让溶液冷却至室温，用旋转蒸发器去除溶剂。在200毫升乙酸乙酯中重新溶解残留物，然后倒入分离漏斗中。用50毫升的去离子水和盐水清洗有机层，将有机层干燥硫酸钠。重力过滤溶液通过硅胶去除干燥剂，然后用200毫升乙酸乙酯冲洗硅胶。在真空下从滤物中去除溶剂，获得无色固体化合物1。在使用前在真空下干燥产品过夜。接下来，在装有搅拌棒的100毫升圆底烧瓶中溶解0.50克醋酸钠，在20毫升的冰川醋酸中溶解。加入1.25克3氟磷酸氢和1.14克谷氨酸，在回流搅拌6小时，获得化合物3的紫色溶液。让混合物冷却至室温，然后倒入100毫升的去维化水中，搅拌10分钟，沉淀化合物3。通过过滤收集固体，用水和石油醚清洗，并在真空中干燥两天。接下来，将0.83克化合物三和20毫升干二甲基硫化物放在50毫升的施伦克烧瓶中，搅拌两分钟。加入0.22克α欧米茄二胺链接剂化合物6和1.05毫升N，N-二异丙基胺，并在90摄氏度的砷下搅拌混合物18小时，在深绿色的混合物中获得同源8。让混合物冷却至室温，倒入100毫升去压水中。将产品提取成乙酸乙酯的三个50毫升部分，将有机层混合，用50毫升水和盐水清洗。将洗净的有机层干燥硫酸钠，过滤掉干燥剂，在真空下去除溶剂。在少量色谱溶剂中重新溶解残留物，并应用于硅胶柱进行纯化。收集荧光产品馏分，将它们混合，并去除溶剂，以获得 Homodimer 8 作为黄色固体。首先，在100毫升的圆底烧瓶中溶解2.28克谷氨酰胺1在25毫升二甲基甲酰胺中。在此溶液中悬浮 2.76 克碾磨碳酸钾。然后，将0.62毫升的碘胺放入装有20针的注射器中。在 10 秒内添加碘烷滴。用橡胶隔膜塞开烧瓶，并加入通风针。在室温下对混合物进行两个小时的声波化，以获得谷氨酸化合物2。用50毫升乙酸乙酯稀释混合物，倒入分离漏斗中。再用50毫升乙酸乙酯将烧瓶冲洗到漏斗中。处理产品，用硅胶柱色谱进行净化，获得谷氨酸2作为无色固体。比较谷氨酸化合物1和2的保留时间，确认N-甲基化成功。要开始验证，用感兴趣的化合物治疗多发性骨髓瘤细胞。分离相关蛋白质，并准备样品进行蛋白质降解的西式 Blot 分析。然后，为SDS-PAGE准备一个凝胶三明治，然后用pH 8.9三轮车-HCl溶液填充阳极缓冲罐。将蛋白质样品加载到凝胶中，以 70 伏特运行 20 分钟，然后运行 115 伏特 150 分钟。接下来，准备1x转移缓冲液进行免疫印迹，并小心地将凝胶从盒式转移到转移缓冲液以平衡。当您从盒式磁带上取出凝胶以进行平衡时，必须非常小心，因为它会很快爆裂和皱褶。将0.45微米聚乙烯二氟化物膜浸入纯甲醇中至少20秒，以激活它，然后浸入1倍转移缓冲液中。让凝胶和膜平衡10分钟。然后，组装西印盒，并应用180毫安百分90分钟，将蛋白质转移到膜上。之后，通过免疫污染来可视化蛋白质。为了评估对细胞生存能力的影响，首先，在生物三酯的96孔板中，每孔播种5万个多发性骨髓瘤细胞。将含有DMSO的介质添加到每井100微升，或化合物8、化合物9或波马利多米德的0.1、1或10微摩尔。为了进行细胞生存能力救援实验，在加入一个微摩尔解poalidomide之前或之后，用化合物8的100纳米摩尔溶液治疗细胞3小时。在5%的二氧化碳大气中，在37摄氏度下孵育细胞24、48或96小时，并用发光测定测量细胞的生存能力。用质子和碳 NMR 确认了同源 PROTAC 8 的结构。异质PROTAC 9被合成为负对，因为谷氨酸部分内的N甲基化导致Cereblon或CRBN的结合能力丧失。同性 PROTAC 8 诱导近乎完全的原体 CRBN 降解，对淋巴转录因子 IKZF1 和 IKZF3 的影响最小。相比之下，异质PROTAC 9表现出与波马利多米德相似的行为。化合物8诱导的CRBN降解可以通过蛋白酶体的直接抑制剂阻止，或间接阻止纯酶抑制。使用化合物8进行预处理的细胞显著抵制了多巴利多米德对IKZF1和IKZF3的影响。化合物8诱导CRBN降解对多发性骨髓瘤细胞在96小时后生存能力的影响比化合物9和poalidomide的IKZF1和IKZF3降解小得多。与未经治疗的细胞相比，使用化合物8进行预处理的多发性骨髓瘤细胞在接触波巴利多米德时具有显著更高的生存能力，这表明化合物8可用于模拟免疫调节 IMiD 耐药性。我们发现，化合物8诱导Cereblon完全蛋白酶体降解，对IKZF1和IKZF3细胞的生存能力和增殖无副作用。将项目技术扩展到其他目标有可能对与癌症和其他疾病有关的蛋白质进行检测和跟踪。当将这种技术应用于其他药物和蛋白质时，应仔细研究药物的分子结构和蛋白质靶点，以选择最佳的连链接剂和附件。IMiDs在小鼠中不起作用，因为Cereblon的点突变，但存在一个转基因敲击小鼠模型，可用于进一步的动物研究。由于波马利多胺是一种模拟沙利度胺，这是高度致畸性，我们不建议孕妇使用这些药物。

Research

JoVE Journal

Chemistry

Origami Inspired Self-assembly of Patterned and Reconfigurable Particles

折纸灵感的图案和可重构颗粒自组装

There are numerous techniques such as photolithography, electron-beam lithography and soft-lithography that can be used to precisely pattern two ...

科研

化学

Isolation and Chemical Characterization of Lipid A from Gram-negative Bacteria

隔离和脂质A的化学表征革兰氏阴性菌

Lipopolysaccharide (LPS) is the major cell surface molecule of gram-negative bacteria, deposited on the outer leaflet of the outer membrane bilayer. LPS ...

Preparing Adherent Cells for X-ray Fluorescence Imaging by Chemical Fixation

化学固定准备贴壁细胞的X射线荧光成像

X-ray fluorescence imaging allows us to non-destructively measure the spatial distribution and concentration of multiple elements simultaneously over ...

Chemical Vapor Deposition of an Organic Magnet, Vanadium Tetracyanoethylene

化学气相沉积的有机磁体，钒四氰

Recent progress in the field of organic materials has yielded devices such as organic light emitting diodes (OLEDs) which have advantages not found in ...

Preparation of Highly Porous Coordination Polymer Coatings on Macroporous Polymer Monoliths for Enhanced Enrichment of Phosphopeptides

对磷酸增强富集制备高度多孔配位聚合物涂层的孔聚合物石柱的

We describe a protocol for the preparation of hybrid materials based on highly porous coordination polymer coatings on the internal surface of macroporous ...

Preparation of Macroporous Epitaxial Quartz Films on Silicon by Chemical Solution Deposition

化学溶液沉积在硅外延大孔石英薄膜的制备

This work describes the detailed protocol for preparing piezoelectric macroporous epitaxial quartz films on silicon(100) substrates. This is a three-step ...

Epitaxial Growth of Perovskite Strontium Titanate on Germanium via Atomic Layer Deposition

锗通过原子层沉积钙钛矿型钛酸锶的外延生长

Atomic layer deposition (ALD) is a commercially utilized deposition method for electronic materials. ALD growth of thin films offers thickness control and ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

使用Photoredox催化剂蠕虫状胶束的简便合成可见光介导的分散聚合

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...