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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
DC Field | Value | Language |
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dc.contributor.author | Lee, Haein | - |
dc.contributor.author | Park, Geunhwa | - |
dc.contributor.author | Kim, Seulha | - |
dc.contributor.author | Son, Boram | - |
dc.contributor.author | Joo, Jinmyoung | - |
dc.contributor.author | Park, Hee Ho | - |
dc.contributor.author | Park, Tai Hyun | - |
dc.date.accessioned | 2023-04-18T06:21:23Z | - |
dc.date.available | 2023-04-18T06:21:23Z | - |
dc.date.created | 2022-11-25 | - |
dc.date.created | 2022-11-25 | - |
dc.date.created | 2022-11-25 | - |
dc.date.created | 2022-11-25 | - |
dc.date.created | 2022-11-25 | - |
dc.date.issued | 2022-11 | - |
dc.identifier.citation | Applied Microbiology and Biotechnology, Vol.106 No.22, pp.7531-7545 | - |
dc.identifier.issn | 0175-7598 | - |
dc.identifier.uri | https://hdl.handle.net/10371/190030 | - |
dc.description.abstract | 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. | - |
dc.language | 영어 | - |
dc.publisher | Springer Verlag | - |
dc.title | Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19α protein | - |
dc.title.alternative | Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19 alpha protein | - |
dc.type | Article | - |
dc.identifier.doi | 10.1007/s00253-022-12218-0 | - |
dc.citation.journaltitle | Applied Microbiology and Biotechnology | - |
dc.identifier.wosid | 000867552100001 | - |
dc.identifier.scopusid | 2-s2.0-85139967486 | - |
dc.citation.endpage | 7545 | - |
dc.citation.number | 22 | - |
dc.citation.startpage | 7531 | - |
dc.citation.volume | 106 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Park, Tai Hyun | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | CELL-PENETRATING PEPTIDES | - |
dc.subject.keywordPlus | ESCHERICHIA-COLI | - |
dc.subject.keywordPlus | ARGININOSUCCINATE SYNTHETASE | - |
dc.subject.keywordPlus | INTRACELLULAR DELIVERY | - |
dc.subject.keywordPlus | SILKWORM HEMOLYMPH | - |
dc.subject.keywordPlus | SOLUBLE EXPRESSION | - |
dc.subject.keywordPlus | FUSION EXPRESSION | - |
dc.subject.keywordPlus | TUMOR-CELLS | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordAuthor | Arginine deiminase (ADI) | - |
dc.subject.keywordAuthor | Melanoma | - |
dc.subject.keywordAuthor | Solubility enhancer | - |
dc.subject.keywordAuthor | Enzyme stabilizer | - |
dc.subject.keywordAuthor | Cell-penetrating protein | - |
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