Design strategy for serine hydroxymethyltransferase probes based on retro-aldol-type reaction.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30787298.
- Also identified by DOI 10.1038/s41467-019-08833-7 and PMC identifier 6382819.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Serine hydroxymethyltransferase (SHMT) is an enzyme that catalyzes the reaction that converts serine to glycine. It plays an important role in one-carbon metabolism. Recently, SHMT has been shown to be associated with various diseases. Therefore, SHMT has attracted attention as a biomarker and drug target. However, the development of molecular probes responsive to SHMT has not yet been realized. This is because SHMT catalyzes an essential yet simple reaction; thus, the substrates that can be accepted into the active site of SHMT are limited. Here, we focus on the SHMT-catalyzed retro-aldol reaction rather than the canonical serine-glycine conversion and succeed in developing fluorescent and <sup>19</sup>F NMR molecular probes. Taking advantage of the facile and direct detection of SHMT, the developed fluorescent probe is used in the high-throughput screening for human SHMT inhibitors, and two hit compounds are obtained.
Medical subject headings
- Aldehydes
- Glycine Hydroxymethyltransferase
- Molecular Probes