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

(2020) In silico design of two novel fusion proteins, p28-IL-24 and p28-M4, targeted to breast cancer cells. Research in Pharmaceutical Sciences. pp. 200-208. ISSN 1735-5362

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Abstract

Background and purpose: An anticancer peptide P28, has shown to be cytolethal on various cancer cells including breast cancer. Moreover, p28 can be alsoused as a targeting moiety in the structure of fusion proteins. IL-24 (or its truncated form, M4) is a cytokine with anticancer activity against a wide range of tumor cells. We aimed at production of a fusion protein consisted of p28 and either IL-24 or M4 to target breast cancer. However, selection of a proper linker to join the two moieties without intervening each other's function is a key factor in the construction of fusion proteins. In the present study, the impact of different linkers on construction of the two chimeric proteins (p28-IL-24 and p28-M4) was assessed in silico. Experimental approach: After selection of some linkers with different lengths and characteristics, a small library of the chimeric proteins was created and assessed. Furthermore, following selection of the most suitable linker, the three-dimensional structures and dynamic behavior of both fusion proteins were evaluated byhomology modeling and molecular dynamic simulation, respectively. Findings / Results: Based on the results, a rigid linker having the peptide sequences of AEAAAKEAAAKA showed highest freedom of action for both moieties. Conclusion and implications: Between the p28-IL-24 and p28-M4 fusion proteins, the former showed better stability as well as solubility and might show stronger anticancer effects in vitro and in vivo, because its peptide moieties showed to exert their activities freely.

Item Type: Article
Keywords: p28 IL-24 fusion protein Homology modeling Molecular Dynamic Simulation Breast cancer MOLECULAR-DYNAMICS CHIMERIC PROTEIN MDA-7/IL-24 SIMULATION STABILITY APOPTOSIS PEPTIDE GROMACS AZURIN DOMAIN
Subjects: QU Biochemistry. Cell Biology and Genetics > QU55-70 Proteins. Amino Acids. Peptides
QZ Pathology > QZ 200-380 Neoplasms
WP Gynecology and Obstetrics > WP 800-910 Breast
Divisions: Faculty of Pharmacy and Pharmaceutical Sciences > Department of Pharmaceutical Biotechnology
Page Range: pp. 200-208
Journal or Publication Title: Research in Pharmaceutical Sciences
Journal Index: ISI
Volume: 15
Number: 2
Identification Number: https://doi.org/10.4103/1735-5362.283820
ISSN: 1735-5362
Depositing User: Zahra Otroj
URI: http://eprints.mui.ac.ir/id/eprint/12610

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