Review
Biochemistry & Molecular Biology
Sara Martin-Villanueva, Gabriel Gutierrez, Dieter Kressler, Jesus de la Cruz
Summary: Ubiquitin is a highly conserved small protein in eukaryotes that functions as a post-translational modifier through ubiquitination. It plays a crucial role in ribosome biogenesis and function, along with other ubiquitin-like proteins such as SUMO. The fusion of ubiquitin moieties to specific ribosomal proteins is evolutionarily significant and helps regulate cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Shaswati Mandal, Guy Mann, Gandhesiri Satish, Ashraf Brik
Summary: The fusion of modified cell-penetrating peptides with synthetic protein analogues can enhance the uptake efficiency of fluorescently labelled proteins in live cells, offering potential for functional studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Plant Sciences
Konstantin Kerner, Soshichiro Nagano, Annika Lubbe, Ute Hoecker
Summary: The study found that the WD repeat of SPA1 is essential for the activity of COP1/SPA, while the WD repeat of COP1 is partially dispensable. A complex with four SPA1-WDs is more active than a complex with only two SPA1-WDs.
PLANT CELL AND ENVIRONMENT
(2021)
Review
Engineering, Chemical
Ikuhiko Nakase
Summary: Researchers found that inducing macropinocytosis through modification with biofunctional peptides on exosomal membranes enhances the cellular uptake of exosomes. Arginine-rich cell-penetrating peptides and EGFR activation have been shown to induce macropinocytosis, providing insights for the development of new strategies for exosomes.
Article
Multidisciplinary Sciences
Kendi Okuda, Miriam Maria Silva Costa Franco, Ari Yasunaga, Ricardo Gazzinelli, Michel Rabinovitch, Sara Cherry, Neal Silverman
Summary: Leishmania parasites utilize virulence mechanisms to invade and replicate in macrophages, inhibiting host defenses and altering gene expression to enhance their survival and replication.
Article
Chemistry, Multidisciplinary
Yan Zhao, Haolin Jiang, Jiazhen Yu, Luyao Wang, Juanjuan Du
Summary: Currently, the clinical application of protein/peptide therapeutics is limited to the extracellular spaces, mainly due to the endosomal entrapment of internalized proteins/peptides. This study presents a strategy to design peptides that enable the delivery from endosomes to cytosol by extending the histidine switch principle. By replacing the Arg/Lys residues in cationic cell-penetrating peptides (CPPs) with histidine, the researchers obtained peptides with pH-dependent membrane-perturbation activity, mimicking the endosomal escape of CPPs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Lei Ding, Guangyu Rong, Yiyun Cheng
Summary: Fluorous tagged peptides have shown promising features for biomedical applications such as drug delivery and multimodal imaging. The bioconjugation of fluoroalkyl ligands onto cargo peptides greatly enhances their proteolytic stability and membrane penetration via a proposed fluorine effect. The tagged peptides also efficiently deliver other biomolecules such as DNA and siRNA into cells via a co-assembly strategy.
MACROMOLECULAR BIOSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Julio C. Y. Liu, Ulrike Kuhbacher, Nicolai B. Larsen, Nikoline Borgermann, Dimitriya H. Garvanska, Ivo A. Hendriks, Leena Ackermann, Peter Haahr, Irene Gallina, Claire Guerillon, Emma Branigan, Ronald T. Hay, Yoshiaki Azuma, Michael Lund Nielsen, Julien P. Duxin, Niels Mailand
Summary: The study reveals that the SUMO-targeted ubiquitin ligase RNF4 plays a major role in ubiquitylation and proteasomal clearance of SUMOylated DPCs in the absence of DNA replication. SUMO modifications of DPCs do not affect their rapid degradation during DNA replication, but provide a critical salvage mechanism to remove DPCs formed after replication. The absence of the SUMO-RNF4 pathway leads to accumulation of unresolved DPCs, causing defective chromosome segregation and cell death during mitosis.
Article
Pharmacology & Pharmacy
Bareera Qamar, Melani Solomon, Alexander Marin, Thomas R. Fuerst, Alexander K. Andrianov, Silvia Muro
Summary: Achieving intracellular delivery of protein therapeutics is a significant challenge. This study investigated the use of ionic polyphosphazenes to deliver protein cargo intracellularly, finding that PZ-PYR showed faster internalization and higher uptake levels in endothelial cells compared to PZ-PEG, although both polymers achieved similar uptake levels in cancer cells. Uptake was mediated by endocytosis through multiple mechanisms.
Article
Chemistry, Multidisciplinary
Ji Liu, Jinhan Sheng, Leihou Shao, Qizhen Zheng, Wenting Li, Xianghan Chen, Lanqun Mao, Ming Wang
Summary: Hierarchical self-assembly of TPE-featured metal-organic cages and beta-cyclodextrin-conjugated polyethylenimine generates fluorescent supramolecular nanoparticles (FSNPs) for efficient protein delivery into neural cells, allowing rapid release into the cytosol for subcellular targeting. Delivery of molecular chaperone DJ-1 using FSNPs activates MAPK/ERK signaling in neural cells to protect cells from oxidative stress.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Biotechnology & Applied Microbiology
Ilaria Porello, Francesco Cellesi
Summary: Achieving effective delivery of therapeutic proteins to intracellular targets is crucial for advancing human health. Current methods, such as chemical modification and nanocarrier-based approaches, have limitations in efficiency and safety. Developing more versatile delivery tools that trigger endocytosis or directly deliver proteins to the cytosol is essential for successful therapeutic effects. This article provides an overview of current methods for intracellular protein delivery, highlighting challenges and opportunities for future research.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Siyuan Yu, Han Yang, Tingdong Li, Haifeng Pan, Shuling Ren, Guoxing Luo, Jinlu Jiang, Linqi Yu, Binbing Chen, Yali Zhang, Shaojuan Wang, Rui Tian, Tianying Zhang, Shiyin Zhang, Yixin Chen, Quan Yuan, Shengxiang Ge, Jun Zhang, Ningshao Xia
Summary: The authors present an intracellular protein delivery system that overcomes the limitations of ineffective endosomal escape and low serum tolerance associated with cell-penetrating peptide-mediated protein delivery. This system shows efficient delivery and therapeutic efficacy in a liver failure model, highlighting the potential of using multifunctional chimaeric peptides for developing cell-penetrating peptide-based protein delivery systems.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Marina Buyanova, Dehua Pei
Summary: Intracellular protein-protein interactions are challenging targets for traditional drug modalities. Macrocyclic peptides have proven to be effective inhibitors, but they are generally impermeable to the cell membrane. Recent advances in MP science and technology have allowed for the development of cell-permeable MPs that can modulate intracellular PPI targets.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Teiko Komori Nomura, Kazuki Heishima, Nobuhiko Sugito, Ryota Sugawara, Hiroshi Ueda, Akao Yukihiro, Ryo Honda
Summary: A new strategy for designing RAS inhibitors through intracellular delivery of RBD has been proposed, demonstrating specific inhibition of oncogenic RAS. The cell-permeable pan-RAS inhibitor Pen-cRaf-v1 effectively targets various RAS mutants and exhibits comparable anticancer activity to a leading pan-RAS inhibitor. This study highlights the feasibility of treating RAS-mutant cancers by targeting oncogenic RAS through intracellular delivery of RBD.
CELL CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jiaying Song, Christina Cortez-Jugo, Steven J. Shirbin, Zhixing Lin, Shuaijun Pan, Greg G. Qiao, Frank Caruso
Summary: This study introduces two template-mediated strategies for immobilizing SNAPPs in microcapsules, achieving sustained release and high antimicrobial activity, internalization by alveolar macrophages in vitro, with negligible cytotoxicity and potential application in pulmonary delivery of antimicrobials against respiratory bacterial infections.
ADVANCED FUNCTIONAL MATERIALS
(2022)