Functionalization of Human Serum Albumin by Tyrosine Click
Human serum albumin (HSA) is a promising drug delivery carrier. Although covalent modification of Cys34 is a well-established method, it is desirable to develop a novel covalent modification method that targets residues other than cysteine to introduce multiple functions into a single HSA molecule....
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8676 |
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| author | Satsuki Obara Keita Nakane Chizu Fujimura Shusuke Tomoshige Minoru Ishikawa Shinichi Sato |
| author_facet | Satsuki Obara Keita Nakane Chizu Fujimura Shusuke Tomoshige Minoru Ishikawa Shinichi Sato |
| author_sort | Satsuki Obara |
| collection | DOAJ |
| description | Human serum albumin (HSA) is a promising drug delivery carrier. Although covalent modification of Cys34 is a well-established method, it is desirable to develop a novel covalent modification method that targets residues other than cysteine to introduce multiple functions into a single HSA molecule. We developed a tyrosine-selective modification of HSA. Three tyrosine selective modification methods, hemin-catalyzed, horseradish peroxidase (HRP)-catalyzed, and laccase-catalyzed reactions were performed, and the modification efficiencies and modification sites of the modified HSAs obtained by these methods were evaluated and compared. We found that the laccase-catalyzed method could efficiently modify the tyrosine residue of HSA under mild reaction conditions without inducing oxidative side reactions. An average of 2.2 molecules of functional groups could be introduced to a single molecule of HSA by the laccase method. Binding site analysis using mass spectrometry suggested Y84, Y138, and Y401 as the main modification sites. Furthermore, we evaluated binding to ibuprofen and found that, unlike the conventional lysine residue modification, the inhibition of drug binding was minimal. These results suggest that tyrosine-residue selective chemical modification is a promising method for covalent drug attachment to HSA. |
| first_indexed | 2024-03-10T08:44:52Z |
| format | Article |
| id | doaj.art-7e7be93f13bf4900a44bd979debe57a0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:52Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7e7be93f13bf4900a44bd979debe57a02023-11-22T07:58:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216867610.3390/ijms22168676Functionalization of Human Serum Albumin by Tyrosine ClickSatsuki Obara0Keita Nakane1Chizu Fujimura2Shusuke Tomoshige3Minoru Ishikawa4Shinichi Sato5Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanFrontier Research Institute for Interdisciplinary Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanHuman serum albumin (HSA) is a promising drug delivery carrier. Although covalent modification of Cys34 is a well-established method, it is desirable to develop a novel covalent modification method that targets residues other than cysteine to introduce multiple functions into a single HSA molecule. We developed a tyrosine-selective modification of HSA. Three tyrosine selective modification methods, hemin-catalyzed, horseradish peroxidase (HRP)-catalyzed, and laccase-catalyzed reactions were performed, and the modification efficiencies and modification sites of the modified HSAs obtained by these methods were evaluated and compared. We found that the laccase-catalyzed method could efficiently modify the tyrosine residue of HSA under mild reaction conditions without inducing oxidative side reactions. An average of 2.2 molecules of functional groups could be introduced to a single molecule of HSA by the laccase method. Binding site analysis using mass spectrometry suggested Y84, Y138, and Y401 as the main modification sites. Furthermore, we evaluated binding to ibuprofen and found that, unlike the conventional lysine residue modification, the inhibition of drug binding was minimal. These results suggest that tyrosine-residue selective chemical modification is a promising method for covalent drug attachment to HSA.https://www.mdpi.com/1422-0067/22/16/8676tyrosine clickhuman serum albumindrug bindinglaccasemodification site |
| spellingShingle | Satsuki Obara Keita Nakane Chizu Fujimura Shusuke Tomoshige Minoru Ishikawa Shinichi Sato Functionalization of Human Serum Albumin by Tyrosine Click International Journal of Molecular Sciences tyrosine click human serum albumin drug binding laccase modification site |
| title | Functionalization of Human Serum Albumin by Tyrosine Click |
| title_full | Functionalization of Human Serum Albumin by Tyrosine Click |
| title_fullStr | Functionalization of Human Serum Albumin by Tyrosine Click |
| title_full_unstemmed | Functionalization of Human Serum Albumin by Tyrosine Click |
| title_short | Functionalization of Human Serum Albumin by Tyrosine Click |
| title_sort | functionalization of human serum albumin by tyrosine click |
| topic | tyrosine click human serum albumin drug binding laccase modification site |
| url | https://www.mdpi.com/1422-0067/22/16/8676 |
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