Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment
Background: 4Z,15Z-bilirubin-IXα (BR), an endogenous toxic compound that is sparingly soluble in water, binds human serum albumin (HSA) with high affinity in a flexible manner. Our previous findings suggest that both Lys195 and Lys199 in subdomain IIA are important for the high-affinity binding of B...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
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Elsevier BV
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/18060 |
| _version_ | 1848749636240539648 |
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| author | Minomo, Ai Ishima, Yu Chuang, Victor Suwa, Yoshiaki Kragh-Hansen, Ulrich Narisoko, Toru Morioka, Hiroshi Maruyama, Toru Otagiri, Masaki |
| author_facet | Minomo, Ai Ishima, Yu Chuang, Victor Suwa, Yoshiaki Kragh-Hansen, Ulrich Narisoko, Toru Morioka, Hiroshi Maruyama, Toru Otagiri, Masaki |
| author_sort | Minomo, Ai |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Background: 4Z,15Z-bilirubin-IXα (BR), an endogenous toxic compound that is sparingly soluble in water, binds human serum albumin (HSA) with high affinity in a flexible manner. Our previous findings suggest that both Lys195 and Lys199 in subdomain IIA are important for the high-affinity binding of BR, and especially Lys199 in stand-alone domain II plays a prominent role in the renal elimination of BR. Our hypothesis is that HSA-domain II with high BR binding would be a useful therapeutic agent to treat hyperbilirubinemia in patients with impaired liver function. Methods: Unbound BR concentrations were determined using a modified HRP assay. To evaluate the effect of pan3_3-13 domain II mutant in promoting urinary BR excretion, the serum concentration and urinary excretion amount of BR were determined using bile duct ligation mice. Results: After three or six rounds of panning, pan3_3-13 and pan6_4 were found to have a significantly higher affinity for BR than wild-type domain II. Administration of pan3_3-13 significantly reduced serum BR level and increased its urinary excretion in the disease model mice as compared to wild-type domain II treatment. Conclusions: These results suggest that pan3_3-13 has great potential as a therapeutic agent that promotes urinary BR excretion in hyperbilirubinemia. |
| first_indexed | 2025-11-14T07:24:05Z |
| format | Journal Article |
| id | curtin-20.500.11937-18060 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:24:05Z |
| publishDate | 2013 |
| publisher | Elsevier BV |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-180602017-09-13T15:44:33Z Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment Minomo, Ai Ishima, Yu Chuang, Victor Suwa, Yoshiaki Kragh-Hansen, Ulrich Narisoko, Toru Morioka, Hiroshi Maruyama, Toru Otagiri, Masaki Background: 4Z,15Z-bilirubin-IXα (BR), an endogenous toxic compound that is sparingly soluble in water, binds human serum albumin (HSA) with high affinity in a flexible manner. Our previous findings suggest that both Lys195 and Lys199 in subdomain IIA are important for the high-affinity binding of BR, and especially Lys199 in stand-alone domain II plays a prominent role in the renal elimination of BR. Our hypothesis is that HSA-domain II with high BR binding would be a useful therapeutic agent to treat hyperbilirubinemia in patients with impaired liver function. Methods: Unbound BR concentrations were determined using a modified HRP assay. To evaluate the effect of pan3_3-13 domain II mutant in promoting urinary BR excretion, the serum concentration and urinary excretion amount of BR were determined using bile duct ligation mice. Results: After three or six rounds of panning, pan3_3-13 and pan6_4 were found to have a significantly higher affinity for BR than wild-type domain II. Administration of pan3_3-13 significantly reduced serum BR level and increased its urinary excretion in the disease model mice as compared to wild-type domain II treatment. Conclusions: These results suggest that pan3_3-13 has great potential as a therapeutic agent that promotes urinary BR excretion in hyperbilirubinemia. 2013 Journal Article http://hdl.handle.net/20.500.11937/18060 10.1016/j.bbagen.2013.01.006 Elsevier BV restricted |
| spellingShingle | Minomo, Ai Ishima, Yu Chuang, Victor Suwa, Yoshiaki Kragh-Hansen, Ulrich Narisoko, Toru Morioka, Hiroshi Maruyama, Toru Otagiri, Masaki Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment |
| title | Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment |
| title_full | Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment |
| title_fullStr | Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment |
| title_full_unstemmed | Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment |
| title_short | Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment |
| title_sort | albumin domain ii mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment |
| url | http://hdl.handle.net/20.500.11937/18060 |