Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/87931
DC Field | Value | Language |
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dc.contributor | Department of Applied Biology and Chemical Technology | - |
dc.creator | Chung, SF | - |
dc.creator | Kim, CF | - |
dc.creator | Kwok, SY | - |
dc.creator | Tam, SY | - |
dc.creator | Chen, YW | - |
dc.creator | Chong, HC | - |
dc.creator | Leung, SL | - |
dc.creator | So, PK | - |
dc.creator | Wong, KY | - |
dc.creator | Leung, YC | - |
dc.creator | Lo, WH | - |
dc.date.accessioned | 2020-09-04T00:52:53Z | - |
dc.date.available | 2020-09-04T00:52:53Z | - |
dc.identifier.uri | http://hdl.handle.net/10397/87931 | - |
dc.language.iso | en | en_US |
dc.publisher | Molecular Diversity Preservation International (MDPI) | en_US |
dc.rights | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). | en_US |
dc.rights | The following publication Chung S-F, Kim C-F, Kwok S-Y, Tam S-Y, Chen YW, Chong H-C, Leung S-L, So P-K, Wong K-Y, Leung Y-C, Lo W-H. Mono-PEGylation of a Thermostable Arginine-Depleting Enzyme for the Treatment of Lung Cancer. International Journal of Molecular Sciences. 2020; 21(12):4234, is available at https://doi.org/10.3390/ijms21124234 | en_US |
dc.subject | L-Arg | en_US |
dc.subject | Mono-PEGylation | en_US |
dc.subject | Thermostable enzyme | en_US |
dc.title | Mono-PEGylation of a thermostable Arginine-depleting enzyme for the treatment of lung cancer | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.volume | 21 | - |
dc.identifier.issue | 12 | - |
dc.identifier.doi | 10.3390/ijms21124234 | - |
dcterms.abstract | L-arginine (L-Arg) depletion induced by randomly PEGylated arginine deiminase (ADI-PEG20) can treat arginosuccinate synthase (ASS)-negative cancers, and ADI-PEG20 is undergoing phase III clinical trials. Unfortunately, ASS-positive cancers are resistant to ADI-PEG20. Moreover, the yield of ADI production is low because of the formation of inclusion bodies. Here, we report a thermostable arginine-depleting enzyme, Bacillus caldovelox arginase mutant (BCA-M: Ser161->Cys161). An abundant amount of BCA-M was easily obtained via high cell-density fermentation and heat treatment purification. Subsequently, we prepared BCA-M-PEG20, by conjugating a single 20 kDa PEG monomer onto the Cys161 residue via thio-chemistry. Unlike ADI-PEG20, BCA-M-PEG20 significantly inhibited ASS-positive lung cancer cell growth. Pharmacodynamic studies showed that a single intraperitoneal injection (i.p). administration of 250 U/mouse of BCA-M-PEG20 induced low L-Arg level over 168 h. The mono-PEGylation of BCA-M prolonged its elimination half-life from 6.4 to 91.4 h (a 14-fold increase). In an A549 lung cancer xenograft model, a weekly administration of 250 U/mouse of BCA-M-PEG20 suppressed tumor growth significantly. We also observed that BCA-M-PEG20 did not cause any significant safety issue in mouse models. Overall, BCA-M-PEG20 showed excellent results in drug production, potency, and stability. Thereby, it has great potential to become a promising candidate for lung cancer therapy. | - |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | International journal of molecular sciences, 2020, v. 21, no. 12, | - |
dcterms.isPartOf | International journal of molecular sciences | - |
dcterms.issued | 2020 | - |
dc.identifier.scopus | 2-s2.0-85086686011 | - |
dc.identifier.pmid | 32545874 | - |
dc.identifier.eissn | 1422-0067 | - |
dc.description.validate | 202009 bcma | - |
dc.description.oa | Version of Record | en_US |
dc.identifier.FolderNumber | OA_Scopus/WOS | en_US |
dc.description.pubStatus | Published | en_US |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
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Chung_Mono-PEGylation_thermostable.pdf | 1.19 MB | Adobe PDF | View/Open |
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