دورية أكاديمية
Computational Design of Novel Cyclic Peptides Endowed with Autophagy-Inhibiting Activity on Cancer Cell Lines
| العنوان: | Computational Design of Novel Cyclic Peptides Endowed with Autophagy-Inhibiting Activity on Cancer Cell Lines |
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| المؤلفون: | Marco Albani, Enrico Mario Alessandro Fassi, Roberta Manuela Moretti, Mariangela Garofalo, Marina Montagnani Marelli, Gabriella Roda, Jacopo Sgrignani, Andrea Cavalli, Giovanni Grazioso |
| المصدر: | International Journal of Molecular Sciences, Vol 25, Iss 9, p 4622 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | peptide, LC3B, autophagy inhibitors, cancer, Atg8, LIR motif, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | (1) Autophagy plays a significant role in development and cell proliferation. This process is mainly accomplished by the LC3 protein, which, after maturation, builds the nascent autophagosomes. The inhibition of LC3 maturation results in the interference of autophagy activation. (2) In this study, starting from the structure of a known LC3B binder (LIR2-RavZ peptide), we identified new LC3B ligands by applying an in silico drug design strategy. The most promising peptides were synthesized, biophysically assayed, and biologically evaluated to ascertain their potential antiproliferative activity on five humans cell lines. (3) A cyclic peptide (named Pep6), endowed with high conformational stability (due to the presence of a disulfide bridge), displayed a Kd value on LC3B in the nanomolar range. Assays accomplished on PC3, MCF-7, and A549 cancer cell lines proved that Pep6 exhibited cytotoxic effects comparable to those of the peptide LIR2-RavZ, a reference LC3B ligand. Furthermore, it was ineffective on both normal prostatic epithelium PNT2 and autophagy-defective prostate cancer DU145 cells. (4) Pep6 can be considered a new autophagy inhibitor that can be employed as a pharmacological tool or even as a template for the rational design of new small molecules endowed with autophagy inhibitory activity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 58732233 |
| العلاقة: | https://www.mdpi.com/1422-0067/25/9/4622Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms25094622 |
| الوصول الحر: | https://doaj.org/article/58732233297a4e25b1dad2b9454abd9bTest |
| رقم الانضمام: | edsdoj.58732233297a4e25b1dad2b9454abd9b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 58732233 |
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| DOI: | 10.3390/ijms25094622 |