Omid Vakili 1 , Seyyed Hossein Khatami 2 , Amir Maleksabet 3 , Ahmad Movahedpour 4 , Saeed Ebrahimi Fana 5 , Rasoul Sadegh 6 , Amir Hossein Salmanzadeh 6 , Hadi Razeghifam 6 , Sajjad Nourdideh 6 , Sadra Samavarchi Tehrani 5 , Mortaza Taheri-Anganeh 4 Show Affiliations »
Abstract
BACKGROUND: Methotrexate (MTX) is a general chemotherapeutic agent utilized to treat a variety of malignancies, woefully, its high doses can cause nephrotoxicity and subsequent defect in the process of MTX excretion. The recombinant form of glucarpidase is produced by engineered E. coli and is a confirmed choice to overcoming this problem. OBJECTIVE: In the present study, in silico analyses were performed to select suitable SPs for the secretion of recombinant glucarpidase in E. coli. METHODS: The signal peptide website and UniProt database were employed to collect the SPs and protein sequences. In the next step, SignalP-5.0 helped us to predict the SPs and the position of cleavage sites. Moreover, physicochemical properties and solubility were evaluated using Prot- Param and Protein-sol online software, and finally, ProtCompB was used to predict the final subcellular localization. RESULTS: Luckily, all SPs could form soluble fusion proteins. At last, it was found that PPB and TIBA could translocate the glucarpidase into the extracellular compartment. CONCLUSION: This study showed that there are only 2 applicable SPs for the extracellular translocation of glucarpidase. Although the findings were remarkable with high degrees of accuracy and precision based on the utilization of bioinformatics analyses, additional experimental assessments are required to confirm and validate it. Recent patents revealed several inventions related to the clinical aspects of vaccine peptides against human disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
BACKGROUND: Methotrexate (MTX) is a general chemotherapeutic agent utilized to treat a variety of malignancies, woefully, its high doses can cause nephrotoxicity and subsequent defect in the process of MTX excretion. The recombinant form of glucarpidase is produced by engineered E. coli and is a confirmed choice to overcoming this problem. OBJECTIVE: In the present study, in silico analyses were performed to select suitable SPs for the secretion of recombinant glucarpidase in E. coli. METHODS: The signal peptide website and UniProt database were employed to collect the SPs and protein sequences. In the next step, SignalP-5.0 helped us to predict the SPs and the position of cleavage sites. Moreover, physicochemical properties and solubility were evaluated using Prot- Param and Protein-sol online software, and finally, ProtCompB was used to predict the final subcellular localization. RESULTS: Luckily, all SPs could form soluble fusion proteins. At last, it was found that PPB and TIBA could translocate the glucarpidase into the extracellular compartment. CONCLUSION: This study showed that there are only 2 applicable SPs for the extracellular translocation of glucarpidase. Although the findings were remarkable with high degrees of accuracy and precision based on the utilization of bioinformatics analyses, additional experimental assessments are required to confirm and validate it. Recent patents revealed several inventions related to the clinical aspects of vaccine peptides against human disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities: Chemical
Keywords:
Methotrexate; bioinformatics; biopharmaceuticals; glucarpidase; malignancies.; recombinant protein
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Year: 2021
PMID： 34547999 DOI： 10.2174/1872208315666210921095420
Source DB: PubMed Journal: Recent Pat Biotechnol ISSN： 1872-2083