Synthesis of 5′-Thymidine-Conjugated Formylphenylboronic Acids as Potential Lysine Targeting Iminoboronate Reversible Covalent Enzyme Probes
The design of reversible-covalent molecules to selectively target the ε-amino functionality of lysine residues in enzymes or proteins is a highly desirable goal. Herein, we describe synthetic methodology used to prepare a series of 5′-thymidine-linked formylphenylboronic acids as probes to interroga...
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| Published in: | Journal of organic chemistry Vol. 87; no. 21; pp. 13542 - 13555 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
American Chemical Society
04-11-2022
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | The design of reversible-covalent molecules to selectively target the ε-amino functionality of lysine residues in enzymes or proteins is a highly desirable goal. Herein, we describe synthetic methodology used to prepare a series of 5′-thymidine-linked formylphenylboronic acids as probes to interrogate sugar nucleotide processing enzymes that recognize thymidine. The first synthetic strategy mitigated the need for protecting group manipulations of thymidine by capitalizing upon the straightforward preparation, isolation, and reactivity of 5′-azidothymidine. An alkyne cycloaddition partner was installed through either a propargyl or ethynyl phenyl ketone derived boronic acid. The second strategy directly linked formylphenylboronic acids to 5-thymidine through an ether linkage installed using Mitsunobu conditions with 3′-O,3-dibenzoylthymidine. Iminoboronate formation was observed with a selected probe. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0022-3263 1520-6904 |
| DOI: | 10.1021/acs.joc.2c01000 |