Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site.
A novel methodology is described for the efficient and divergent synthesis of pseudodisaccharides, molecules comprising of amino carbasugar analogues linked to natural sugars. The methodology is general and enables the introduction of diversity both at the carbasugar and the natural sugar components...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3832595?pdf=render |
| _version_ | 1828875668923875328 |
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| author | Victoria Vinader Mohamed H Haji-Abdullahi L H Patterson Kamyar Afarinkia |
| author_facet | Victoria Vinader Mohamed H Haji-Abdullahi L H Patterson Kamyar Afarinkia |
| author_sort | Victoria Vinader |
| collection | DOAJ |
| description | A novel methodology is described for the efficient and divergent synthesis of pseudodisaccharides, molecules comprising of amino carbasugar analogues linked to natural sugars. The methodology is general and enables the introduction of diversity both at the carbasugar and the natural sugar components of the pseudodisaccharides. Using this approach, a series of pseudodisaccharides are synthesised that mimic the repeating backbone unit of heparan sulfate, and are tested for inhibition of heparanase, a disease-relevant enzyme that hydrolyses heparan sulfate. A new homology model of human heparanase is described based on a family 79 β-glucuronidase. This model is used to postulate a computational rationale for the observed activity of the different pseudodisaccharides and provide valuable information that informs the design of potential inhibitors of this enzyme. |
| first_indexed | 2024-12-13T08:03:39Z |
| format | Article |
| id | doaj.art-c13261046a6d496f80aae91b9c420cf6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T08:03:39Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c13261046a6d496f80aae91b9c420cf62022-12-21T23:54:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8211110.1371/journal.pone.0082111Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site.Victoria VinaderMohamed H Haji-AbdullahiL H PattersonKamyar AfarinkiaA novel methodology is described for the efficient and divergent synthesis of pseudodisaccharides, molecules comprising of amino carbasugar analogues linked to natural sugars. The methodology is general and enables the introduction of diversity both at the carbasugar and the natural sugar components of the pseudodisaccharides. Using this approach, a series of pseudodisaccharides are synthesised that mimic the repeating backbone unit of heparan sulfate, and are tested for inhibition of heparanase, a disease-relevant enzyme that hydrolyses heparan sulfate. A new homology model of human heparanase is described based on a family 79 β-glucuronidase. This model is used to postulate a computational rationale for the observed activity of the different pseudodisaccharides and provide valuable information that informs the design of potential inhibitors of this enzyme.http://europepmc.org/articles/PMC3832595?pdf=render |
| spellingShingle | Victoria Vinader Mohamed H Haji-Abdullahi L H Patterson Kamyar Afarinkia Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site. PLoS ONE |
| title | Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site. |
| title_full | Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site. |
| title_fullStr | Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site. |
| title_full_unstemmed | Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site. |
| title_short | Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site. |
| title_sort | synthesis of a pseudo disaccharide library and its application to the characterisation of the heparanase catalytic site |
| url | http://europepmc.org/articles/PMC3832595?pdf=render |
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