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 |
1 | Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases | Acta Pharmaceutica Sinica BAvailable online 25 September 2022... | 温州医科大学 | 小分子 |
2 | Mechanism investigation of Caspase-8/GSDMC dependent immunogenic cell death induced by Ophiopogonin B in NSCLC cells | Pharmacological Research - Modern Chinese Medicine29 August 2022... | 南京中医药大学 | 小分子 |
3 | Fragments of bombinakinin M exist in lipopolysaccharide-stimulated skin secretions of Bombina maxima and show lipopolysaccharide-neutralizing activity | Journal of Immunological Methods25 August 2022... | 昆明医科大学第一附属医院 | 小分子 |
4 | Oxidized tea polyphenol (OTP-3) targets EGFR synergistic nimotuzumab at inhibition of non-small cell lung tumor growth | Bioorganic Chemistry6 August 2022... | 云南农业大学 | 小分子 |
5 | A preliminary cumulative risk assessment of Diethylhexyl phthalate and Dibutyl phthalate based on the inhibition of embryonic development via the PPARγ pathway | Toxicology in Vitro25 July 2022... | 国家食品安全风险评估中心 | 小分子 |
6 | Inhibiting STAT5 signaling pathway by natural products for cancer prevention and therapy: In vitro and in vivo activity and mechanisms of action | Pharmacological Research19 July 2024... | 浙江中医药大学 | 小分子 |
7 | Optimizing component formula suppresses lung cancer by blocking DTL-mediated PDCD6 ubiquitination to regulate the MAPK/JNK pathway | Journal of Ethnopharmacology15 July 2024... | 南京中医药大学 | 小分子 |
8 | Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studies | Bioorganic Chemistry7 July 2022... | 贵州医科大学 | 小分子 |
9 | Discovery of Isoform-Selective Akt3 Degraders Overcoming Osimertinib-Induced Resistance in Non-Small Cell Lung Cancer Cells | Journal of Medicinal Chemistry | 暨南大学 | 小分子 |
10 | AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis | Nature Communications volume 13, Article number: 4499 (2022) | 南京大学 | 小分子 |
11 | Discovery of 2-(1-(3-Chloro-4-cyanophenyl)-1H-pyrazol-3-yl)acetamides as Potent, Selective, and Orally Available Antagonists Targeting the Androgen Receptor | J. Med. Chem. 2022 | 浙江大学 | 小分子 |
12 | PDTAC: Targeted Photodegradation of GPX4 Triggers Ferroptosis and Potent Antitumor Immunity | J. Med. Chem. 2022, 65, 18, 12176–12187 | 北京大学 | 小分子 |
13 | Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13 | J. Med. Chem. 2022, 65, 16, 11066–11083 | 暨南大学 | 小分子 |
14 | Selective Photoaffinity Probe for Monitoring Farnesoid X Receptor Expression in Cultured Cells | Anal. Chem. 2022, 94, 30, 10722–10729 | 中国药科大学 | 小分子 |
15 | Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88-Dependent Inflammation | https://doi.org/10.1002/advs.202202590 | 温州医科大学 | 小分子 |
16 | Substrate-induced dimerization of elaiophylin glycosyltransferase reveals a novel self-activating form of glycosyltransferase for symmetric glycosylation | Acta Crystallographica Section D | Guangzhou Institutes of Biomedicine and Health, | 小分子 |
17 | Calycosin protects against oxidative stress-induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2 | https://doi.org/10.1002/ptr.7591 | the Second Affiliated Hospital of Guangzhou Medical University | 小分子 |
18 | Vegetable-derived indole enhances the melanoma-treating efficacy of chemotherapeutics | https://doi.org/10.1002/ptr.7565 | 南京中医药大学 | 小分子 |
19 | Crucial role of Ca2+/CN signalling pathway in the antifungal activity of disenecioyl-cis-khellactone against Botrytis cinerea | https://doi.org/10.1002/ps.7085 | 江苏省中国科学院植物研究所 | 小分子 |
20 | [Progress of target determination and mechanism of bioactive components of traditional Chinese medicine] | Zhongguo Zhongyao Zazhi | 北京中医药大学 | 小分子 |
21 | Galangin Exhibits Neuroprotective Effects in 6-OHDA-Induced Models of Parkinson’s Disease via the Nrf2/Keap1 Pathway | Pharmaceuticals 2022, 15(8), 1014 | 西南医科大学 | 小分子 |
22 | A Small-Molecule Inhibitor of the Anthranilyl-CoA Synthetase PqsA for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa | Antimicrobial Chemotherapy | 浙江工业大学 | 小分子 |
23 | Interaction of RAGE with α-synuclein fibrils mediates inflammatory response of microglia | Cell Reports20 September 2022... | 中国科学院上海有机化学研究所 | 蛋白 |
24 | Sequence difference of angiotensin-converting enzyme 2 between nonhuman primates affects its binding-affinity with SARS-CoV-2 S receptor binding domain | Biosafety and HealthAvailable online 9 September 2022... | 中国生物技术股份有限公司 | 蛋白 |
25 | The mechanisms of immune response and evasion by the main SARS-CoV-2 variants | iScience2 September 2022... | 浙江中医药大学 | 蛋白 |
26 | SIRT1 activation synergizes with FXR agonism in hepatoprotection via governing nucleocytoplasmic shuttling and degradation of FXR | Acta Pharmaceutica Sinica BAvailable online 27 August 2022... | 中国药科大学 | 蛋白 |
27 | An emerging paradigm to develop analytical methods based on immobilized transmembrane proteins and its applications in drug discovery | TrAC Trends in Analytical Chemistry4 July 2022... | 西北大学 | 蛋白 |
28 | Metabolic pathway assembly using docking domains from type I cis-AT polyketide synthases | Nature Communications volume 13, Article number: 5541 (2022) | Shenzhen Institute of Synthetic Biology | 蛋白 |
29 | Insulin induces insulin receptor degradation in the liver through EphB4 | Nature Metabolism volume 4, pages1202–1213 (2022) | Chinese Academy of Medical Sciences and Peking Union Medical College | 蛋白 |
30 | Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors | Oncogene volume 41, pages4754–4767 (2022) | 上海生物化学与细胞生物学研究所 | 蛋白 |
31 | LDLR, LRP1, and Megalin redundantly participate in the uptake of Clostridium novyi alpha-toxin | Communications Biology volume 5, Article number: 906 (2022) | 西湖大学 | 蛋白 |
32 | Structural insights into partner selection for MYB and bHLH transcription factor complexes | Nature Plants volume 8, pages1108–1117 (2022 | 复旦大学 | 蛋白 |
33 | APOE interacts with ACE2 inhibiting SARS-CoV-2 cellular entry and inflammation in COVID-19 patients | Signal Transduction and Targeted Therapy volume 7, | 厦门大学 | 蛋白 |
34 | Exploring the Binding Affinity and Mechanism between ACE2 and the Trimers of Delta and Omicron Spike Proteins by Molecular Dynamics Simulation and Bioassay | J. Chem. Inf. Model. 2022, 62, 18, 4512–4522 | 中国科学院上海药物研究所 | 蛋白 |
35 | Insight into Thermodynamic and Kinetic Profiles in Small-Molecule Optimization | J. Med. Chem. 2022, 65, 16, 10809–10847 | 中国药科大学 | 蛋白 |
36 | Third-Generation Covalent TMP-Tag for Fast Labeling and Multiplexed Imaging of Cellular Proteins |
| 北京大学 | 蛋白 |
37 | Structures, biomimetic synthesis, and anti-SARS-CoV-2 activity of two pairs of enantiomeric phenylpropanoid-conjugated protoberberine alkaloids from the rhizomes of Corydalis decumbens | Archives of Pharmacal Research volume 45, pages631–643 (2022) | 澳门科技大学 | 蛋白 |
38 | Screening and Characterization of Shark-Derived VNARs against SARS-CoV-2 Spike RBD Protein | Int. J. Mol. Sci. 2022, 23(18), 10904 | 集美大学 | 蛋白 |
39 | The Generation of Dual-Targeting Fusion Protein PD-L1/CD47 for the Inhibition of Triple-Negative Breast Cancer | Biomedicines 2022, 10(8), 1843 | 上海交通大学 | 蛋白 |
40 | Development of a thermostable SARS-CoV-2 variant-based bivalent protein vaccine with cross-neutralizing potency against Omicron subvariants | Virology20 September 2022... | 北京义翘神州科技股份有限公司 | 抗体 |
41 | SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope | Nature Microbiology volume 7, pages1635–1649 (2022) | Guangzhou Institutes of Biomedicine and Health | 抗体 |
42 | Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth | Nature Communications volume 13, Article number: 5552 (2022) | 西湖大学 | 抗体 |
43 | A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery | Signal Transduction and Targeted Therapy volume 7, Article number: 301 (2022) | 中国科学院武汉病毒研究所 | 抗体 |
44 | Structural insights into auxin recognition and efflux by Arabidopsis PIN1. | Nature volume 609, pages611–615 (2022) | 中国科学技术大学 | 抗体 |
45 | Branched Polyethylenimine as a Carrier for Significantly Improving the Biopanning Efficiency of Phages Specific to Hapten | ACS Appl. Polym. Mater. 2022, 4, 8, 5737–5745 | 中国海洋大学 | 抗体 |
46 | Novel hKDR mouse model depicts the antiangiogenesis and apoptosis-promoting effects of neutralizing antibodies targeting vascular endothelial growth factor receptor 2 | https://doi.org/10.1111/cas.15594 | National Institutes for Food and Drug Control (NIFDC) | 抗体 |
47 | Novel application of anti-human Fc nanobody for screening high-producing CHO cells for monoclonal antibody | https://doi.org/10.1002/elsc.202200028 | Shanghai Bao Pharmaceuticals Co., Ltd., | 抗体 |
48 | Development of a variant of dinutuximab with enhanced antitumor efficacy and reduced induction of neuropathic pain | https://doi.org/10.1002/2211-5463.13464 | Shanghai Mabstone Biotechonology | 抗体 |
49 | A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode | Journal of Nanobiotechnology volume 20, Article number: 411 (2022) | The Affiliated Hospital of Qingdao University | 抗体 |
50 | Structural Basis of a Novel Agonistic Anti-OX40 Antibody. | Biomolecules 2022, 12(9), 1209 | 丁浮靶点 | 抗体 |
51 | Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer | Structural Biology | 复旦大学 | 抗体 |
52 | Anti-mesothelin CAR-T immunotherapy in patients with ovarian cancer | Cancer Immunology, Immunotherapy (2022) | 南京师范大学 | 抗体 |
53 | Aptasensing a class of small molecules based on split aptamers and hybridization chain reaction-assisted AuNPs nanozyme | Food Chemistry29 August 2022... | 中国海洋大学 | DNA |
54 | Ricin aptamer screening based on the QSAR model and construction of piezoresistive micro-cantilever aptasensor | Talanta18 August 2022... | 民用nbc防护国家重点实验室 | DNA |
55 | One-step high-throughput detection of low-abundance biomarker BDNF using a biolayer interferometry-based 7D aptasensor | Biosensors and Bioelectronics14 July 2026... | 上海耳鼻喉医院 | DNA |
56 | Biochemical and structural characterization of a KTSC family single-stranded DNA-binding protein from Euryarchaea | International Journal of Biological Macromolecules7 July 2022... | Chinese PLA General Hospital First Medical Center | DNA |
57 | A facile and integrated aptamer-based platform for preliminary and simultaneous screening of group targets | Sensors and Actuators B: Chemical3 July 2022... | 中国海洋大学 | DNA |
58 | A Label-Free Colorimetric Aptasensor Containing DNA Triplex Molecular Switch and AuNP Nanozyme for Highly Sensitive Detection of Saxitoxin | Journal of Ocean University of China volume 21, pages1343–1350 (2022 |
| DNA |
59 | Optimization of Gonyautoxin1/4-Binding G-Quadruplex Aptamers by Label-Free Surface-Enhanced Raman Spectroscopy | Toxins 2022, 14(9), 622; https://doi.org/10.3390/toxins14090622 | 海军军医大学 | DNA |
60 | Evolution of Interferon-Gamma Aptamer with Good Affinity and Analytical Utility by a Rational In Silico Base Mutagenesis Post-SELEX Strategy | Beijing University of Chemical Technology | 北京化工大学 | DNA |
61 | CDKN2AIP is critical for spermiogenesis and germ cell development | Cell & Bioscience volume 12 | Zhongnan Hospital of Wuhan University | DNA |
62 | Long non-coding RNA DARS-AS1 promotes tumor progression by directly suppressing PACT-mediated cellular stress | Communications Biology volume 5, Article number: 822 (2022) | 清华大学 | RNA |
63 | An anti-picornaviral strategy based on the crystal structure of foot-and-mouth disease virus 2C protein | Cell Reports5 July 2022... | Chinese Academy of Medical Sciences and Peking Union Medical College | 多肽 |
64 | Succinylation Inhibits the Enzymatic Hydrolysis of the Extracellular Matrix Protein Fibrillin 1 and Promotes Gastric Cancer Progression | https://doi.org/10.1002/advs.202200546 | First Affiliated Hospital of Nanjing Medical University | 多肽 |
65 | BTApep-TAT peptide inhibits ADP-ribosylation of BORIS to induce DNA damage in cancer | Molecular Cancer volume 21, Article number: 158 (2022) | 杭州医学院 | 多肽 |
66 | EGF promotes PKM2 O-GlcNAcylation by stimulating O-GlcNAc transferase phosphorylation at Y976 and their subsequent association | Journal of Biological Chemistry3 August 2022... | 东北师范大学 | 多糖 |
67 | A Sulfated Abalone Polysaccharide Inhibited SARS-CoV-2 Infection of Vero E6 Cells In Vitro | Foods 2022, 11(18), 2865 | 大连工业大学 | 多糖 |
68 | Research trends in biomedical applications of two-dimensional nanomaterials over the last decade – A bibliometric analysis | Advanced Drug Delivery Reviews12 July 2022... | National Center for Nanoscience and Technology | 垂钓 |
69 | In situ analysis of nanoparticle soft corona and dynamic evolution | Nature Communications volume 13, Article number: 5389 (2022) | Institute of High Energy Physics & National Center for Nanoscience and Technology of China | 垂钓 |
70 | Morphology-driven protein corona manipulation for preferential delivery of lipid nanodiscs | Nano Today11 September 2022... | 上海市静安区中心医院 | |
71 | A nanomaterial targeting the spike protein captures SARS-CoV-2 variants and promotes viral elimination | Nature Nanotechnology volume 17, pages993–1003 (2022) | 中国科学院深圳先进技术研究院 | 纳米材料 |
72 | Glucose sensing by regulator of G protein signaling 1 (RGS1) plays a crucial role in coordinating defense in response to environmental variation in tomato | https://doi.org/10.1111/nph.18356 | 浙江大学 | 细胞 |
73 | Simultaneous Maturation of Single Chain Antibody Stability and Affinity by CHO Cell Display | Bioengineering 2022, 9(8), 360 | 中科院生物物理研究所 | 定量 |
74 | Re-understanding of structure and anticoagulation: Fucosylated chondroitin sulfate from sea cucumber Ludwigothurea grisea | Carbohydrate Polymers5 July 2022... | 中南民族大学 | 蔗糖 |
75 | Identifying the Epitopes of Bacillus thuringiensis Cry2Aa Toxin Involved in Cadherin Interaction by a Monoclonal Antibody | Applied Biochemistry and Biotechnology (2022) | 南京农业大学 |
|
76 | Cryo-EM structure of the human IgM B cell receptor | SCIENCE VOL. 377 | 西湖大学 |
|