Next Article in Journal
Glycosylation and Characterization of Human Transferrin in an End-Stage Kidney Disease
Next Article in Special Issue
Synthesis of Ethyl Pyrimidine-Quinolincarboxylates Selected from Virtual Screening as Enhanced Lactate Dehydrogenase (LDH) Inhibitors
Previous Article in Journal
Verification of AKT and CDK5 Gene and RNA Interference Combined with Irradiation to Mediate Fertility Changes in Plutella xylostella (Linnaeus)
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 25
Issue 9
10.3390/ijms25094622
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Computational Design of Novel Cyclic Peptides Endowed with Autophagy-Inhibiting Activity on Cancer Cell Lines

by
Marco Albani
1,
Enrico Mario Alessandro Fassi
1,*,
Roberta Manuela Moretti
2,
Mariangela Garofalo
3,
Marina Montagnani Marelli
2,
Gabriella Roda
1,
Jacopo Sgrignani
4,
Andrea Cavalli
4,5 and
Giovanni Grazioso
1,*
1
Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy
2
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy
3
Department of Pharmaceutical and Pharmacological Sciences, Università di Padova, Via F. Marzolo 5, 35131 Padova, Italy
4
Institute for Research in Biomedicine (IRB), Via Chiesa 5, 6500 Bellinzona, Switzerland
5
Swiss Institute of Bioinformatics (SIB), University of Lausanne, Quartier UNIL-Sorge, Bâtiment Amphipôle, 1015 Lausanne, Switzerland
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(9), 4622; https://doi.org/10.3390/ijms25094622
Submission received: 26 March 2024 / Revised: 17 April 2024 / Accepted: 21 April 2024 / Published: 24 April 2024
(This article belongs to the Special Issue Drug Discovery: Design, Synthesis and Activity Evaluation)
Browse Figures
Review Reports Versions Notes

Abstract

(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.
Keywords: peptide; LC3B; autophagy inhibitors; cancer; Atg8; LIR motif peptide; LC3B; autophagy inhibitors; cancer; Atg8; LIR motif
Graphical Abstract

Share and Cite

MDPI and ACS Style

Albani, M.; Fassi, E.M.A.; Moretti, R.M.; Garofalo, M.; Montagnani Marelli, M.; Roda, G.; Sgrignani, J.; Cavalli, A.; Grazioso, G. Computational Design of Novel Cyclic Peptides Endowed with Autophagy-Inhibiting Activity on Cancer Cell Lines. Int. J. Mol. Sci. 2024, 25, 4622. https://doi.org/10.3390/ijms25094622

AMA Style

Albani M, Fassi EMA, Moretti RM, Garofalo M, Montagnani Marelli M, Roda G, Sgrignani J, Cavalli A, Grazioso G. Computational Design of Novel Cyclic Peptides Endowed with Autophagy-Inhibiting Activity on Cancer Cell Lines. International Journal of Molecular Sciences. 2024; 25(9):4622. https://doi.org/10.3390/ijms25094622

Chicago/Turabian Style

Albani, Marco, Enrico Mario Alessandro Fassi, Roberta Manuela Moretti, Mariangela Garofalo, Marina Montagnani Marelli, Gabriella Roda, Jacopo Sgrignani, Andrea Cavalli, and Giovanni Grazioso. 2024. "Computational Design of Novel Cyclic Peptides Endowed with Autophagy-Inhibiting Activity on Cancer Cell Lines" International Journal of Molecular Sciences 25, no. 9: 4622. https://doi.org/10.3390/ijms25094622

APA Style

Albani, M., Fassi, E. M. A., Moretti, R. M., Garofalo, M., Montagnani Marelli, M., Roda, G., Sgrignani, J., Cavalli, A., & Grazioso, G. (2024). Computational Design of Novel Cyclic Peptides Endowed with Autophagy-Inhibiting Activity on Cancer Cell Lines. International Journal of Molecular Sciences, 25(9), 4622. https://doi.org/10.3390/ijms25094622

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop