Q3|国内BLI文献盘点:小分子研究愈发火热
第三季度结束了,又到了陈老湿交季报的时间。第三季度国内采用生物层干涉技术(BLI)发表的文章依旧维持了高速增长的趋势,共发表超过80篇文章,同比增长60%。文章的单位和应用方向,陈老湿也做了小结。其中诸如南京中医药大学、中国药科大学和西湖大学等十几个单位发表的文章在两篇以上,详见下表(76篇):单位数量单位数量南京中医药大学3上海生化所1中国药科大学3中国科学院高能物理研究所1西湖大学3武汉病毒所1温州医科大学2清华大学1浙江中医药大学2南京大学1中国海洋大学2中国科学技术大学1中国医学科学院北京协和医学院2厦门大学1暨南大学2上海药物所1广州生物医药与健康研究院2中国食品药品检定研究院1深圳先进技术研究院2广州医科大学第二附属医院1复旦大学2上海宝济药业有限公司1浙江大学2南京医科大学第一附属医院1北京大学2江苏植物研究所1南京农业大学1上海迈石生物技术有限公司1神州细胞1澳门科技大学1上海有机所1集美大学1复旦大学静安中心医院1大连工业大学1中国中生1青岛大学附属医院1昆明医科大学第一附属医院1青岛海洋科学与技术国家实验室1民用nbc防护国家重点实验室1海军军医大学1云南农业大学1北京化工大学1东北师范大学1北京中医药大学1国家食品安全风险评估中心1丁浮靶点1上海耳鼻喉医院1武汉大学中南医院1国家纳米科学与技术中心1西南医科大学1贵州医科大学1南京师范大学1中国人民解放军总医院第一医疗中心1杭州医学院1中南民族大学1生物物理所1西北大学1上海交通大学1中国海洋大学1浙江工业大学1从应用方向上看,依旧涉及到多个方向。小分子的文章数量逐步提升,超过蛋白和抗体的应用的数量,比例已接近1:3。高速增长的原因主要有几点:BLI技术无流路,对溶剂(DMSO)不敏感,假阳性低,高通量,操作简单,成本低,仪器稳定性好等优点可以帮助研究人更快,更高质量的获得了小分子检测的结果。不同应用方向文章比例最具影响力Science|全球首个人源IgM同种型B细胞受体复合物高分辨率结构解析西湖大学施一公团队在Science期刊上首次报道了人源IgM同种型B细胞受体(IgM-BCR)的高分辨率三维结构,揭示了膜结合的IgM(mIgM)与Igα和Igβ异源二聚体复合物组装的分子机制,从而回答了B细胞受体如何组装这一重要科学问题。为了稳定IgM-BCR的结构,让其融合了VRC01抗体(一种针对HIV表面蛋白gp120的抗体)。那这个IgM-BCR表达的蛋白有活性码?文章就采用Octet® 非标记分子互作系统检测了其与gp120的结合活性。将IgM-BCR固化在链霉亲和素传感器上,与gp120单体和gp120三聚体结合,三聚体的亲和力较高,产生了明显的亲合作用(多聚体带来的多个位点结合,使得亲和力提高)。最具经济效益全球首个靶向CDK12/13的PROTAC降解剂乳腺癌(BC)是世界上和女性中最常见的癌症之一,其中三阴性的乳腺癌TNBC在乳腺癌中最为棘手。细胞周期蛋白依赖性激酶CDK,是 TNBC 治疗的潜在治疗靶点。以往针对的CDK的靶向药最终会产生耐药抗性,蛋白降解靶向嵌合体PROTAC可以定向降解靶蛋白,PROTAC 可以提高蛋白质降解的选择性并逃避耐药机制。暨南大学丁克团队报道了全球首个靶向CDK12/13的 PROTAC降解剂7f,它能够与 CDK12 和 CDK13 紧密结合,Octet® 检测结果显示7f母本化合物(化合物3,4)与CDK12/13的亲和力分别为 16.2 和 8.6 nM,亲和力高,并表现出出色的激酶组选择性。PROTAC分子与CDK12和CDK13的结合活性检测此外,文中还采用Incucyte® 实时活细胞分析系统长时间分析,发现该PROTAC对MFM223和MDA-MB-231肿瘤细胞具有很强的抗肿瘤活性。Incucyte® 实时检测药物对MFM223和MDA-MB-231肿瘤细胞的抑制生长最巧妙应用Octet® 分子垂钓助力纳米蛋白冠的原位分析近期,国家纳米科学中心陈春英团队采用Octet® 与质谱分析在纳米颗粒表面软蛋白冠原位动态分析方面取得重要突破。该方法通过BLI技术可实时监测蛋白冠的形成、交换和解离过程,通过原位、快速地洗脱多层蛋白冠的组分,实现了软、硬蛋白冠的高效分离、鉴定及时间分辨的动态研究,突破了软蛋白冠分析的技术瓶颈。研究提出的多层蛋白冠的分析新策略将为探究纳米颗粒与生物体相互作用,以及纳米药物的理性设计提供创新分析方法。基于BLI技术的垂钓策略最具“生命”的应用解析基于细胞的Octet® 检测光合作用不仅为植物提供了能量影响植物的生长与发育,也深刻影响植物的抗病性。浙江大学师恺课题组发现由Glc-RGS1-G蛋白信号通路介导的新的光强度相应防御系统,为研究植物细胞如何在不同环境中感知胞外糖、调节防御系统以及提高逆境抗性提供依据。基于细胞的生物层干涉技术,将原生质体(protoplast) 脱去细胞壁的细胞捕获到生物传感器表面,再与待测的糖分子结合,首次发现Glc特异性结合番茄RGS1蛋白,证实Glc诱导RGS1蛋白发生内吞现象;基于BLI技术检测细胞表面的RGS1与不同糖的结合反应小身板,大能量针对新冠病毒双表位鲨鱼纳米抗体筛选与验证常规抗体相比,鲨鱼纳米抗体具有相对分子量小、抗原结合活性高、组织渗透性强、理化性质更稳定且制备成本低等优点。集美大学的研究人员免疫条纹斑竹鲨后,通过噬菌体展示和BLI技术在体外筛选和验证了针对新冠病毒的鲨鱼纳米抗体以及双表位组合抗体。文章使用的Octet® N1分子互作系统只有A4纸大小,一滴样品即可实现分子互作的检测,真正的小身板,大能量。文章海量的动力学、表位和竞争抑制的数据均来自于这台史上“最迷你”的互作仪。文章中大量动力学、表位和竞争抑制的数据Octet® 采用无流路,实时检测的方式,实现了高通量,高精度,低成本的检测,更好的支持了研究人员的基础研究与成果转化。反过来研究人员基于Octet®的灵活性,也不断开发出新的检测应用和方法,更加快速和深入的研究分子作用的机理,探索生命的奥秘!为了能够帮助大家轻松入门,快速了解分子互作市场概况和技术流派,仪器信息网特别组织策划“分子互作分析技术”专题(点击查看)。Q3国内Octet® 文献一览表序号文献题目期刊类别单位名称应用领域1Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseasesActa Pharmaceutica Sinica BAvailable online 25 September 2022...温州医科大学小分子2Mechanism investigation of Caspase-8/GSDMC dependent immunogenic cell death induced by Ophiopogonin B in NSCLC cellsPharmacological Research - Modern Chinese Medicine29 August 2022...南京中医药大学小分子3Fragments of bombinakinin M exist in lipopolysaccharide-stimulated skin secretions of Bombina maxima and show lipopolysaccharide-neutralizing activityJournal of Immunological Methods25 August 2022...昆明医科大学第一附属医院小分子4Oxidized tea polyphenol (OTP-3) targets EGFR synergistic nimotuzumab at inhibition of non-small cell lung tumor growthBioorganic Chemistry6 August 2022...云南农业大学小分子5A preliminary cumulative risk assessment of Diethylhexyl phthalate and Dibutyl phthalate based on the inhibition of embryonic development via the PPARγ pathwayToxicology in Vitro25 July 2022...国家食品安全风险评估中心小分子6Inhibiting STAT5 signaling pathway by natural products for cancer prevention and therapy: In vitro and in vivo activity and mechanisms of actionPharmacological Research19 July 2024...浙江中医药大学小分子7Optimizing component formula suppresses lung cancer by blocking DTL-mediated PDCD6 ubiquitination to regulate the MAPK/JNK pathwayJournal of Ethnopharmacology15 July 2024...南京中医药大学小分子8Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studiesBioorganic Chemistry7 July 2022...贵州医科大学小分子9Discovery of Isoform-Selective Akt3 Degraders Overcoming Osimertinib-Induced Resistance in Non-Small Cell Lung Cancer CellsJournal of Medicinal Chemistry暨南大学小分子10AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesisNature Communications volume 13, Article number: 4499 (2022)南京大学小分子11Discovery of 2-(1-(3-Chloro-4-cyanophenyl)-1H-pyrazol-3-yl)acetamides as Potent, Selective, and Orally Available Antagonists Targeting the Androgen ReceptorJ. Med. Chem. 2022浙江大学小分子12PDTAC: Targeted Photodegradation of GPX4 Triggers Ferroptosis and Potent Antitumor ImmunityJ. Med. Chem. 2022, 65, 18, 12176–12187北京大学小分子13Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13J. Med. Chem. 2022, 65, 16, 11066–11083暨南大学小分子14Selective Photoaffinity Probe for Monitoring Farnesoid X Receptor Expression in Cultured CellsAnal. 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