Development of a novel, high-affinity ssDNA trypsin inhibitor
Inhibitors of serine proteases are not only extremely useful in the basic research but are also applied extensively in clinical settings. Using Systematic Evolution of Ligands by Exponential Enrichment (SELEX) approach we developed a family of novel, single-stranded DNA aptamers capable of specific...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2019-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2019.1569648 |
| _version_ | 1818154647215407104 |
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| author | Stanislaw Malicki Miroslaw Ksiazek Pawel Majewski Aleksandra Pecak Piotr Mydel Przemyslaw Grudnik Grzegorz Dubin |
| author_facet | Stanislaw Malicki Miroslaw Ksiazek Pawel Majewski Aleksandra Pecak Piotr Mydel Przemyslaw Grudnik Grzegorz Dubin |
| author_sort | Stanislaw Malicki |
| collection | DOAJ |
| description | Inhibitors of serine proteases are not only extremely useful in the basic research but are also applied extensively in clinical settings. Using Systematic Evolution of Ligands by Exponential Enrichment (SELEX) approach we developed a family of novel, single-stranded DNA aptamers capable of specific trypsin inhibition. Our most potent candidate (T24) and its short version (T59) were thoroughly characterised in terms of efficacy. T24 and T59 efficiently inhibited bovine trypsin with Ki of 176 nM and 475 nM, respectively. Interestingly, in contrast to the majority of known trypsin inhibitors, the selected aptamers have superior specificity and did not interact with porcine trypsin or any human proteases tested. These included plasmin and thrombin characterised by trypsin-like substrate specificity. Our results demonstrate that SELEX may be successfully employed in the development of potent and specific DNA based protease inhibitors. |
| first_indexed | 2024-12-11T14:29:50Z |
| format | Article |
| id | doaj.art-bdf17d8dea0e4e3a9c78cd0b1d122473 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-11T14:29:50Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-bdf17d8dea0e4e3a9c78cd0b1d1224732022-12-22T01:02:30ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-0134163864310.1080/14756366.2019.15696481569648Development of a novel, high-affinity ssDNA trypsin inhibitorStanislaw Malicki0Miroslaw Ksiazek1Pawel Majewski2Aleksandra Pecak3Piotr Mydel4Przemyslaw Grudnik5Grzegorz Dubin6Jagiellonian UniversityJagiellonian UniversityBiophysics and Biotechnology, Jagiellonian UniversityJagiellonian UniversityBiophysics and Biotechnology, Jagiellonian UniversityJagiellonian UniversityJagiellonian UniversityInhibitors of serine proteases are not only extremely useful in the basic research but are also applied extensively in clinical settings. Using Systematic Evolution of Ligands by Exponential Enrichment (SELEX) approach we developed a family of novel, single-stranded DNA aptamers capable of specific trypsin inhibition. Our most potent candidate (T24) and its short version (T59) were thoroughly characterised in terms of efficacy. T24 and T59 efficiently inhibited bovine trypsin with Ki of 176 nM and 475 nM, respectively. Interestingly, in contrast to the majority of known trypsin inhibitors, the selected aptamers have superior specificity and did not interact with porcine trypsin or any human proteases tested. These included plasmin and thrombin characterised by trypsin-like substrate specificity. Our results demonstrate that SELEX may be successfully employed in the development of potent and specific DNA based protease inhibitors.http://dx.doi.org/10.1080/14756366.2019.1569648aptamerssdnatrypsinprotease inhibitor |
| spellingShingle | Stanislaw Malicki Miroslaw Ksiazek Pawel Majewski Aleksandra Pecak Piotr Mydel Przemyslaw Grudnik Grzegorz Dubin Development of a novel, high-affinity ssDNA trypsin inhibitor Journal of Enzyme Inhibition and Medicinal Chemistry aptamer ssdna trypsin protease inhibitor |
| title | Development of a novel, high-affinity ssDNA trypsin inhibitor |
| title_full | Development of a novel, high-affinity ssDNA trypsin inhibitor |
| title_fullStr | Development of a novel, high-affinity ssDNA trypsin inhibitor |
| title_full_unstemmed | Development of a novel, high-affinity ssDNA trypsin inhibitor |
| title_short | Development of a novel, high-affinity ssDNA trypsin inhibitor |
| title_sort | development of a novel high affinity ssdna trypsin inhibitor |
| topic | aptamer ssdna trypsin protease inhibitor |
| url | http://dx.doi.org/10.1080/14756366.2019.1569648 |
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