دورية أكاديمية
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Atomic Force Microscopy Lifetime Analysis: An Intuitive Method for Evaluating Receptor Tyrosine Kinase Dimer-Targeting Inhibitors.

التفاصيل البيبلوغرافية
العنوان: Atomic Force Microscopy Lifetime Analysis: An Intuitive Method for Evaluating Receptor Tyrosine Kinase Dimer-Targeting Inhibitors.
المؤلفون: Zou Q; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China., Zhang Q; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China., Du B; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China., Wang H; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China., Yang X; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China., Wang Q; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China., Wang K; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China.
المصدر: Analytical chemistry [Anal Chem] 2024 Jul 09; Vol. 96 (27), pp. 10962-10968. Date of Electronic Publication: 2024 Jun 26.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, American Chemical Society.
مواضيع طبية MeSH: Microscopy, Atomic Force* , Protein Kinase Inhibitors*/pharmacology , Protein Kinase Inhibitors*/chemistry , Proto-Oncogene Proteins c-met*/antagonists & inhibitors , Proto-Oncogene Proteins c-met*/metabolism, Humans ; Protein Multimerization/drug effects ; Ligands ; Hepatocyte Growth Factor/metabolism ; Aptamers, Nucleotide/chemistry ; Aptamers, Nucleotide/metabolism
مستخلص: Overexpression of receptor tyrosine kinases (RTKs) or binding to ligands can lead to the formation of specific unliganded and liganded RTK dimers, and these two RTK dimers are potential targets for preventing tumor metastasis. Traditional RTK dimer inhibitor analysis was mostly based on end point assays, which required cumbersome cell handling and behavior monitoring. There are still challenges in developing intuitive process-based analytical methods to study RTK dimer inhibitors, especially those used to visually distinguish between unliganded and liganded RTK dimer inhibitors. Herein, taking the mesenchymal-epithelial transition factor (MET) receptor, an intuitive method for evaluating MET inhibitors has been developed based on atomic force microscopy (AFM) lifetime analysis. The time interval between the start of the force and the bond break point was regarded as the bond lifetime, which could reflect the stability of the MET dimer. The results showed that there was a significant difference in the lifetime (τ) of unliganded MET dimers (τ 1 = 207.87 ± 4.69 ms) and liganded MET dimers (τ 2 = 330.58 ± 15.60 ms) induced by the hepatocyte growth factor, and aptamer SL1 could decrease τ 1 and τ 2 , suggesting that SL1 could inhibit both unliganded and liganded MET dimers. However, heparin only decreased τ 2 , suggesting that it could inhibit only the liganded MET dimer. AFM-based lifetime analysis methods could monitor RTK dimer status rather than provide overall average results, allowing for intuitive process-based analysis and evaluation of RTK dimers and related inhibitors at the single-molecule level. This study provides a novel complementary strategy for simple and intuitive RTK inhibitor research.
المشرفين على المادة: 0 (Protein Kinase Inhibitors)
EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
EC 2.7.10.1 (MET protein, human)
0 (Ligands)
67256-21-7 (Hepatocyte Growth Factor)
0 (Aptamers, Nucleotide)
تواريخ الأحداث: Date Created: 20240626 Date Completed: 20240709 Latest Revision: 20240805
رمز التحديث: 20240806
DOI: 10.1021/acs.analchem.4c01353
PMID: 38925633
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-6882
DOI:10.1021/acs.analchem.4c01353