Targeting Nucleases via Transition State Mimicry
Lead Research Organisation:
UNIVERSITY OF OXFORD
Department Name: Oxford Chemistry
Abstract
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Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/R512060/1 | 30/09/2017 | 30/03/2023 | |||
| 1947555 | Studentship | EP/R512060/1 | 30/09/2017 | 31/12/2021 | Tobias John |
| NE/W502728/1 | 31/03/2021 | 30/03/2022 | |||
| 1947555 | Studentship | NE/W502728/1 | 30/09/2017 | 31/12/2021 | Tobias John |
| Description | Formaldehyde (HCHO), a highly reactive electrophile, is both a human metabolite and a carcinogen above threshold levels. As HCHO is produced during enzymatic reactions in the human cell, a scavenging role for the N-terminal end of proteins was hypothesised. Here, it is shown that the N-terminus of H2B (bearing an N-terimal proline) has an exceptional susceptibility to reactions with HCHO, whilst it doesn't react with similar compounds. The resulting HCHO derived adduct is a fused 5,5-bicycle which is chemically very stable. These results imply that N-terminal prolines on proteins may act as potential sink for genotoxic HCHO. On another project, we investigate N-terminal cysteines which also react readiliy with HCHO to form stable adducts. It is conceivable that these reactions inhibit enzymatic activities of proteins that rely on N-terminal cysteines. |
| Exploitation Route | As this is a basic science project, it is important for other researchers to know that N-terminal prolines and cysteines can be influenced by HCHO, as HCHO is often used as additives (e.g. in vaccines). |
| Sectors | Chemicals Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |