دورية أكاديمية
Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19α protein ; Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19 alpha protein
العنوان: | Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19α protein ; Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19 alpha protein |
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المؤلفون: | Lee, Haein, Park, Geunhwa, Kim, Seulha, Son, Boram, Joo, Jinmyoung, Park, Hee Ho, Park, Tai Hyun |
المساهمون: | Park, Tai Hyun |
بيانات النشر: | Springer Verlag |
سنة النشر: | 2022 |
المجموعة: | Seoul National University: S-Space |
مصطلحات موضوعية: | CELL-PENETRATING PEPTIDES, ESCHERICHIA-COLI, ARGININOSUCCINATE SYNTHETASE, INTRACELLULAR DELIVERY, SILKWORM HEMOLYMPH, SOLUBLE EXPRESSION, FUSION EXPRESSION, TUMOR-CELLS, APOPTOSIS, INHIBITION, Arginine deiminase (ADI), Melanoma, Solubility enhancer, Enzyme stabilizer, Cell-penetrating protein |
الوصف: | Arginine deiminase (ADI) is a microbial-derived enzyme which catalyzes the conversion of l-arginine into l-citrulline. ADI originating from Mycoplasma has been reported to present anti-tumor activity against arginine-auxotrophic tumors, including melanoma. Melanoma cells are sensitive to arginine depletion due to reduced expression of argininosuccinate synthase 1 (ASS1), a key enzyme for arginine biosynthesis. However, clinical applications of recombinant ADI for melanoma treatment present some limitations. Since recombinant ADI is not human-derived, it shows instability, proteolytic degradation, and antigenicity in human serum. In addition, there is a problem of drug resistance issue due to the intracellular expression of once-silenced ASS1. Moreover, recombinant ADI proteins are mainly expressed as inclusion body forms in Escherichia coli and require a time-consuming refolding process to turn them back into active form. Herein, we propose fusion of recombinant ADI from Mycoplasma hominis and 30Kc19 alpha, a cell-penetrating protein which also increases stability and soluble expression of cargo proteins, to overcome these problems. We inserted matrix metalloproteinase-2 cleavable linker between ADI and 30Kc19 alpha to increase enzyme activity in melanoma cells. Compared to ADI, ADI-LK-30Kc19 alpha showed enhanced solubility, stability, and cell penetration. The fusion protein demonstrated selective cytotoxicity and reduced drug resistance in melanoma cells, thus would be a promising strategy for the improved efficacy in melanoma treatment. ; N ; 1 |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | unknown |
تدمد: | 0175-7598 |
العلاقة: | Applied Microbiology and Biotechnology, Vol.106 No.22, pp.7531-7545; https://hdl.handle.net/10371/190030Test; 000867552100001; 2-s2.0-85139967486; 176393 |
DOI: | 10.1007/s00253-022-12218-0 |
الإتاحة: | https://doi.org/10.1007/s00253-022-12218-0Test https://hdl.handle.net/10371/190030Test |
رقم الانضمام: | edsbas.6FB4B947 |
قاعدة البيانات: | BASE |
تدمد: | 01757598 |
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DOI: | 10.1007/s00253-022-12218-0 |