In silico design of two novel fusion proteins, p28-IL-24 and p28-M4, targeted to breast cancer cells

Ghavimi, Reza; Mohammadi, Elmira; Akbari, Vajihe; Shafiee, Fatemeh; Jahanian-Najafabadi, Ali

doi:10.4103/1735-5362.283820

Cited by 11 publications

(7 citation statements)

References 34 publications

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“…Cancer is the leading cause of death in developed countries and the second cause of death in developing countries ( 1 , 2 ). The prevalence and mortality of cancer are rapidly growing because of aging, population growth, and predisposing behaviors such as smoking ( 2 , 3 ).…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin

2021

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Cancer is one of the prominent causes of death worldwide. Despite the existence of various modalities for cancer treatment, many types of cancer remain uncured or develop resistance to therapeutic strategies. Furthermore, almost all chemotherapeutics cause a range of side effects because they affect normal cells in addition to malignant cells. Therefore, the development of novel therapeutic agents that are targeted specifically toward cancer cells is indispensable. Immunotoxins (ITs) are a class of tumor cell-targeted fusion proteins consisting of both a targeting moiety and a toxic moiety. The targeting moiety is usually an antibody/antibody fragment or a ligand of the immune system that can bind an antigen or receptor that is only expressed or overexpressed by cancer cells but not normal cells. The toxic moiety is usually a protein toxin (or derivative) of animal, plant, insect, or bacterial origin. To date, three ITs have gained Food and Drug Administration (FDA) approval for human use, including denileukin diftitox (FDA approval: 1999), tagraxofusp (FDA approval: 2018), and moxetumomab pasudotox (FDA approval: 2018). All of these ITs take advantage of bacterial protein toxins. The toxic moiety of the first two ITs is a truncated form of diphtheria toxin, and the third is a derivative of Pseudomonas exotoxin (PE). There is a growing list of ITs using PE, or its derivatives, being evaluated preclinically or clinically. Here, we will review these ITs to highlight the advances in PE-based anticancer strategies, as well as review the targeting moieties that are used to reduce the non-specific destruction of non-cancerous cells. Although we tried to be as comprehensive as possible, we have limited our review to those ITs that have proceeded to clinical trials and are still under active clinical evaluation.

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Section: Introductionmentioning

confidence: 99%

Pseudomonas Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin

2021

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“…To obtain multifunctional nanoparticles for the preparation of a high-efficiency nanovaccine, we first constructed a plasmid pET-CTBSA which could express a basic skeleton monomer lacking any antigen sequence in standard E. coli DH5α cells. Importantly, to ensure the two functional domainscholera toxin B subunit (CTB) and streptavidinof the designed multifunctional nanoparticle can fold correctly, they were connected via a rigid peptide linker (AEAAAKEAAAKA) which has been proven to provide flexibility of action for both moieties of the linkage in previous studies. , After transforming E. coli DH5α with pET-CTBSA and confirming the successfully expression of the fusion monomer (Figure S1), it was further purified by affinity and size-exclusion chromatography. Although Coomassie blue staining and Western blotting results showed that the molecular weight of CTB-SA monomer was about 35 kDa (Figure a), the target protein was eluted in 8–10 mL from a 24 mL column volume of Superdex 200 gel from size-exclusion chromatography (Figure b), indicating that the CTB-SA existed in the form of a polymer.…”

Section: Resultsmentioning

confidence: 99%

Self-Assembled Proteinaceous Nanoparticles for Co-Delivery of Antigens and Cytosine Phosphoguanine (CpG) Adjuvants: Implications for Nanovaccines

Li¹,

Pan²,

Li³

et al. 2023

ACS Appl. Nano Mater.

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Nanotechnology has developed rapidly, giving rise to "nanovaccinology". In particular, protein-based nanocarriers have gained widespread attention because of their excellent biocompatibility. As the development of flexible and rapid vaccines is challenging, modular extensible nanoparticles are urgently needed. In this study, a multifunctional nanocarrier capable of delivering various biomolecules (including polysaccharides, proteins, and nucleic acids) was designed by fusing the cholera toxin B subunit with streptavidin. Then, the nanocarrier was used to prepare a bioconjugate nanovaccine against S. f lexneri by co-delivery of antigens and CpG adjuvants. Subsequent experimental results indicated that the nanovaccine with multiple components could stimulate both adaptive and innate immunity. Moreover, combining nanocarriers and CpG adjuvants with glycan antigens could improve the survival of vaccinated mice during the interval of two vaccination injections. The multifunctional nanocarrier and the design strategy demonstrated in this study could be utilized in the development of many other nanovaccines against infectious diseases.

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“…A specific protease cleavage site is usually inserted in the linker region for the efficient removal of a fusion protein (Malik, 2016). Two strategies are used for the rational designing of fusion proteins; one with the help of a suitable linker and another with an in-silico approach (Ghavimi et al, 2020). Confirmation of the desired linked protein will be done by characterization as shown in figure 1.…”

Section: Strategies For Fusion Protein Designmentioning

confidence: 99%

Linkers: a synergistic way for chimeric proteins

Patel¹,

Menon²,

Patel³

2020

Preprint

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Linkers are short or long stretch of amino acid sequences used to create chimeric proteins. Linkers can adopt various structures in a biological environment which is a deciding factor for the functionality of a chimeric protein. It is essential to generate fully separated proteins in the chimeric protein and an effectual linker design increases the stability and activity of the protein. In this review, we summarize the types of linkers and strategies for designing linkers in chimeric protein generation. Appropriate linker design results in the creation of recombinant fusion protein which can be employed in biochemical analysis, drug targeting, pharmaceuticals, diagnostic, and industrial and biotechnological applications.

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In silico design of two novel fusion proteins, p28-IL-24 and p28-M4, targeted to breast cancer cells

Cited by 11 publications

References 34 publications

Pseudomonas Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin

Pseudomonas Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin

Self-Assembled Proteinaceous Nanoparticles for Co-Delivery of Antigens and Cytosine Phosphoguanine (CpG) Adjuvants: Implications for Nanovaccines

Linkers: a synergistic way for chimeric proteins

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