AI Article Synopsis
- Methotrexate (MTX) is a chemotherapy drug that can cause kidney damage at high doses, but glucarpidase, produced by engineered E. coli, helps mitigate this issue.
- The study aimed to identify suitable signal peptides (SPs) for secreting glucarpidase from E. coli using bioinformatics tools.
- Results showed that two specific SPs, PPB and TIBA, can effectively translocate glucarpidase outside the cell, although further experimental validation is needed to confirm these findings.
Article 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1872208315666210921095420 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Glucarpidase for Treatment of High-Dose Methotrexate Toxicity.
Blood
January 2025
Brigham and Women's Hospital, Boston, Massachusetts, United States.
High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the U.
View Article and Find Full Text PDFA European consensus recommendation on the management of delayed methotrexate elimination: supportive measures, leucovorin rescue and glucarpidase treatment.
J Cancer Res Clin Oncol
October 2024
Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany.
Article Synopsis
- * A panel of European physicians developed consensus statements to guide the prevention and treatment of DME, focusing on using glucarpidase and supportive measures like hyperhydration and urine alkalinization.
- * Early identification of DME is crucial for timely interventions, which may include increased hydration, high-dose leucovorin, and glucarpidase when needed to mitigate risks associated with DME.
Low-Dose Planned Glucarpidase Allows Safe Outpatient High-Dose Methotrexate Treatment for CNS Lymphoma.
JCO Oncol Pract
October 2024
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY.
Article Synopsis
- * A study tested the feasibility of administering HD-MTX in an outpatient setting with the aid of low-dose glucarpidase to help clear the drug more quickly.
- * Results showed that all treatments were effective and safe, with no hospitalizations needed, suggesting that outpatient HD-MTX with glucarpidase could change how CNS lymphoma is treated.
Navigating methotrexate toxicity: Examining the therapeutic roles of folinic acid and glucarpidase.
Br J Clin Pharmacol
June 2024
Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Article Synopsis
- Methotrexate (MTX) toxicity is influenced by factors like dosing frequency, dosage, and administration route, with renal impairment worsening the toxicity.
- Low-dose MTX overdoses are usually safe, but repeated doses and higher doses increase toxicity risk, necessitating different treatments with folinic acid depending on the scenario.
- Glucarpidase can quickly reduce MTX levels in severe cases, especially intrathecal poisoning, but is costly and limited in availability; other supportive therapies like hydration and haemodialysis may also be helpful.
Early intervention is important when administering glucarpidase for methotrexate intoxication. Author's reply.
Eur J Intern Med
June 2024
U.O.C di Medicina Interna con Stroke Care, Dipartimento di Promozione della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (PROMISE), University of Palermo, Sicily, Italy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!