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Synthesis and Evaluation of a Novel c-Met-Targeting Cyclic Peptide as a Potential Diagnostic Agent for Colorectal Cancer.

التفاصيل البيبلوغرافية
العنوان: Synthesis and Evaluation of a Novel c-Met-Targeting Cyclic Peptide as a Potential Diagnostic Agent for Colorectal Cancer.
المؤلفون: Chang Q; State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China., Huang K; State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China., Zou L; State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China., Li A; State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China., Ye Z; State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China., Lin Q; State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China., Gu Y; State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China.
المصدر: Molecular pharmaceutics [Mol Pharm] 2024 Jul 01; Vol. 21 (7), pp. 3613-3622. Date of Electronic Publication: 2024 Jun 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101197791 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1543-8392 (Electronic) Linking ISSN: 15438384 NLM ISO Abbreviation: Mol Pharm Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Chemical Society, c2004-
مواضيع طبية MeSH: Colorectal Neoplasms*/diagnostic imaging , Proto-Oncogene Proteins c-met*/metabolism , Peptides, Cyclic*/chemistry, Humans ; Animals ; Mice ; Cell Line, Tumor ; Mice, Nude ; Tomography, Emission-Computed, Single-Photon/methods ; Mice, Inbred BALB C ; Female ; Xenograft Model Antitumor Assays
مستخلص: The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase linked to the proliferation, survival, invasion, and metastasis of several types of cancers, including colorectal cancer (CRC), particularly when aberrantly activated. Our study strategically designs peptides derived from interactions between c-Met and the antibody Onartuzumab. By utilizing a cyclic strategy, we achieved significantly enhanced peptide stability and affinity. Our in vitro assessments confirmed that the cyclic peptide HYNIC-cycOn exhibited a higher affinity ( K D = 83.5 nM) and greater specificity compared with its linear counterpart. Through in vivo experiments, [ 99m Tc]Tc-HYNIC-cycOn displayed exceptional tumor-targeting capabilities and minimal absorption in nontumor cells, as confirmed by single-photon emission computed tomography. Notably, the ratios of tumor to muscle and tumor to intestine, 1 h postinjection, were 4.78 ± 0.86 and 3.24 ± 0.47, respectively. Comparable ratios were observed in orthotopic CRC models, recording 4.94 ± 0.32 and 3.88 ± 0.41, respectively. In summary, [ 99m Tc]Tc-HYNIC-cycOn shows substantial promise as a candidate for clinical applications. We show that [ 99m Tc]Tc-HYNIC-cycOn can effectively target and visualize c-Met-expressing tumors in vivo , providing a promising approach for enhancing diagnostic accuracy when detecting c-Met in CRC.
فهرسة مساهمة: Keywords: c-Met; colorectal cancer; cyclic peptide
المشرفين على المادة: EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
0 (Peptides, Cyclic)
EC 2.7.10.1 (MET protein, human)
تواريخ الأحداث: Date Created: 20240610 Date Completed: 20240701 Latest Revision: 20240710
رمز التحديث: 20240711
DOI: 10.1021/acs.molpharmaceut.4c00330
PMID: 38853512
قاعدة البيانات: MEDLINE
الوصف
تدمد:1543-8392
DOI:10.1021/acs.molpharmaceut.4c00330