89426-34-6

Usage

Uses

Used in Drug Development:
4-Fluoro-L-threonine serves as a key component in the creation of fluorinated analogs of proteinogenic amino acids. These analogs are valuable for developing new drugs with improved properties, such as enhanced stability, selectivity, and bioavailability. The incorporation of 4-fluoro-L-threonine into drug molecules can lead to the design of more effective therapeutic agents.
Used in Protein-Protein Interaction Studies:
As a structural analog of L-threonine, 4-fluoro-L-threonine is utilized as a tool to investigate the intricacies of protein-protein interactions. By substituting this fluorinated amino acid into proteins, researchers can gain insights into the role of specific amino acids in mediating these interactions, which is crucial for understanding various biological processes and developing targeted therapies.
Used in Structural and Functional Protein Studies:
4-Fluoro-L-threonine plays a significant role in studying the structure and function of proteins. By incorporating this amino acid into proteins, scientists can probe the effects on protein conformation, stability, and activity. This information is vital for elucidating the mechanisms of protein function and for engineering proteins with desired properties.
Used in the Synthesis of Peptidomimetics and Bioactive Compounds:
4-Fluoro-L-threonine has been explored as a building block in the synthesis of peptidomimetics, which are conformationally restricted peptide analogs designed to mimic the bioactive conformation of a native peptide. These peptidomimetics can exhibit enhanced stability, bioavailability, and potency compared to their natural peptide counterparts. Additionally, 4-fluoro-L-threonine contributes to the development of other bioactive compounds with potential applications in medicine and biotechnology.

Upstream product

• 14031-35-7 S-Adenosyl-L-methionine 
• 72-19-5 L-threonine 
• 1544-46-3 2-fluoroacetaldehyde 
• 731-98-6 5’-fluoro-5’-deoxyadenosine 
• 194666-37-0 Benzoic acid (S)-1-((2R,4S)-2-tert-butyl-1-methyl-5-oxo-imidazolidin-4-yl)-2-fluoro-ethyl ester 
• 102608-41-3 t-butyl (4S),(5S)-5-fluoromethyl-2-oxo-4-oxazolidinecarboxylate 

Downstream Products

• 1019-57-4 acetaldehyde 2,4-dinitrophenylhydrazine 
• 17610-81-0 2-Oxobutyric acid 2,4-Dinitrophenylhydrazone 
• 365-69-5 2-fluoroacetaldehyde 2,4-dinitrophenylhydrazone 

Relevant academic research and scientific papers

Defluorination of 4-fluorothreonine by threonine deaminase

4-Fluorothreonine (4-FT) is the only naturally occurring fluorinated amino acid antibiotic. Although two conserved proteins in the 4-FT pathway have been found to be involved in self-detoxification mechanisms, the 4-FT-producing strains may also require an alternative pathway to degrade the intracellular 4-FT. In this study, we examined the possible degradation role of three enzymes involved in threonine metabolite pathways toward 4-FT as a possible degradation route to avoid in vivo 4-FT accumulation. Among these three enzymes, threonine deaminase was found to catalyse a defluorination reaction to generate 4-hydroxy-α-ketobutyrate, which is supposed to be further metabolised by an aldolase that likely is a unique occurrence in the 4-FT-producing strains. Our finding may constitute a 4-FT degradation pathway as a complementary resistance mechanism.

Identification of fluorinases from streptomyces sp MA37, norcardia brasiliensis, and actinoplanes sp N902-109 by genome mining

The fluorinase is an enzyme that catalyses the combination of S-adenosyl-L-methionine (SAM) and a fluoride ion to generate 5′-fluorodeoxy adenosine (FDA) and L-methionine through a nucleophilic substitution reaction with a fluoride ion as the nucleophile. It is the only native fluorination enzyme that has been characterised. The fluorinase was isolated in 2002 from Streptomyces cattleya, and, to date, this has been the only source of the fluorinase enzyme. Herein, we report three new fluorinase isolates that have been identified by genome mining. The novel fluorinases from Streptomyces sp. MA37, Nocardia brasiliensis, and an Actinoplanes sp. have high homology (80-87 % identity) to the original S. cattleya enzyme. They all possess a characteristic 21-residue loop. The three newly identified genes were overexpressed in E. coli and shown to be fluorination enzymes. An X-ray crystallographic study of the Streptomyces sp. MA37 enzyme demonstrated that it is almost identical in structure to the original fluorinase. Culturing of the Streptomyces sp. MA37 strain demonstrated that it not only also elaborates the fluorometabolites, fluoroacetate and 4-fluorothreonine, similar to S. cattleya, but this strain also produces a range of unidentified fluorometabolites. These are the first new fluorinases to be reported since the first isolate, over a decade ago, and their identification extends the range of fluorination genes available for fluorination biotechnology. Get on the fluor! The fluorinase enzyme from Streptomyces cattleya was identified in 2002 as the only fluorination enzyme known in biochemistry. Three additional fluorinases expressed through bacterial genome mining are now reported. These new fluorinases extend the range of genes available for developing fluorination biotechnology. Copyright

Amalgamation of nucleosides and amino acids in antibiotic biosynthesis: Discovery of an l -threonine: Uridine-5′-aldehyde transaldolase

The lipopeptidyl nucleoside antibiotics represented by A-90289, caprazamycin, and muraymycin are structurally highlighted by a nucleoside core that contains a nonproteinogenic β-hydroxy-α-amino acid named 5′-C-glycyluridine (GlyU). Bioinformatic analysis of the biosynthetic gene clusters revealed a shared open reading frame encoding a protein with sequence similarity to serine hydroxymethyltransferases, resulting in the proposal that this shared enzyme catalyzes an aldol-type condensation with glycine and uridine-5′-aldehyde to furnish GlyU. Using LipK involved in A-90289 biosynthesis as a model, we now functionally assign and characterize the enzyme responsible for the C-C bond-forming event during GlyU biosynthesis as an l-threonine:uridine-5′-aldehyde transaldolase. Biochemical analysis revealed this transformation is dependent upon pyridoxal-5′-phosphate, the enzyme has no activity with alternative amino acids, such as glycine or serine, as aldol donors, and acetaldehyde is a coproduct. Structural characterization of the enzyme product is consistent with stereochemical assignment as the threo diastereomer (5′S,6′S)-GlyU. Thus this enzyme orchestrates C-C bond breaking and formation with concomitant installation of two stereocenters to make a new l-α-amino acid with a nucleoside side chain.

A short highly stereoselective synthesis of the fluorinated natural product (2S,3S )-4-fluorothreonine

A three step stereoselective route to the fluorinated natural product (2S,3S)-4-fluorothreonine is described; the route is amenable to the preparation of (2S,3S)-4-fluoro[3-2H]threonine and (2S,3R)-[4,4,4-2H3]threonine.