53186-57-5

Usage

Uses

Used in Analytical Chemistry:
S-adenosyl-3-thiopropylamine is used as a calibrant solution for solid-phase extraction studies in human urine samples. It serves as a reference compound to ensure the accuracy and reliability of the extraction process, which is crucial for obtaining accurate results in various analytical applications.
Used in Capillary Electrophoresis (CE):
S-adenosyl-3-thiopropylamine is used as an analyte in capillary electrophoresis, a widely used separation technique that allows the analysis of various compounds based on their size and charge. Its unique chemical properties make it a suitable analyte for studying the separation efficiency and optimization of CE methods.
Used in Micellar Electrokinetic Chromatography (MEKC):
S-adenosyl-3-thiopropylamine is also used as an analyte in micellar electrokinetic chromatography, a variant of capillary electrophoresis that involves the use of micelles as pseudo-stationary phases. This technique is particularly useful for the separation of neutral and charged analytes, and the compound's properties make it a valuable analyte for studying and optimizing MEKC methods.

Biochem/physiol Actions

S-(5′-Adenosyl)-3-thiopropylamine or S-adenosyl-L-homocysteine comprises base, sugar or amino acid. It acts as an inhibitor for spermidine synthase and spermine synthase.

Upstream product

• 23909-16-2 3-benzylmercaptopropylamine 
• 892-48-8 5'-deoxy-5'-chloroadenosine 
• 3483-12-3 diothiothreitol 
• 109-79-5 n-butanethiol 
• 462-47-5 mercapto-3 propylamine 
• 58-61-7 adenosine 
• 263715-50-0 5'-deoxy-2',3'-O-isopropylidene-5'-[3-(phthalimido)propylthio]adenosine 
• 84365-04-8 5'-acetylthio-5'-deoxy-2',3'-O-isopropylidene adenosine 
• 362-75-4 2',3'-isopropylidene adenosine 
• 115465-32-2 5'-deoxy-5'-[3-(phthalimido)propylthio]adenosine 

Relevant academic research and scientific papers

Efficient synthesis of s-adenosyl-L-homocysteine natural product analogues and their use to elucidate the structural determinant for cofactor binding of the DNA methyltransferase M·HhaI

5'-Acetylthio-5'-deoxy-2',3'-O-isopropylideneadenosine (8) was directly prepared from commercially available 2',3'-O-isopropylideneadenosine (7) and thioacetic acid under Mitsunobu conditions in almost quantitative yield. In situ cleavage of the acetylthio function of 8 followed by coupling with different alkyl bromides proceeded with high yields. Deprotection of the obtained 5'-thionucleosides yielded the S-adenosyl-L-homocysteine analogues decarboxylated AdoHcy (11), deaminated AdoHcy (14) and 5'- [3(cyano)propylthio]-5'-deoxyadenosine (16) in good overall yields. Direct deprotection of the thionucleoside 8 delivered 5'-thio-5'-deoxyadenosine (18) in excellent yield. In addition, binding constants of these AdoHcy analogues and the DNA methyltransferase M·HhaI were determined in a fluorescence assay.

Substrate-Dependent Cleavage Site Selection by Unconventional Radical S-Adenosylmethionine Enzymes in Diphthamide Biosynthesis

S-Adenosylmethionine (SAM) has a sulfonium ion with three distinct C-S bonds. Conventional radical SAM enzymes use a [4Fe-4S] cluster to cleave homolytically the C5′,adenosine-S bond of SAM to generate a 5′-deoxyadenosyl radical, which catalyzes various downstream chemical reactions. Radical SAM enzymes involved in diphthamide biosynthesis, such as Pyrococcus horikoshii Dph2 (PhDph2) and yeast Dph1-Dph2 instead cleave the Cγ,Met-S bond of methionine to generate a 3-amino-3-carboxylpropyl radical. We here show radical SAM enzymes can be tuned to cleave the third C-S bond to the sulfonium sulfur by changing the structure of SAM. With a decarboxyl SAM analogue (dc-SAM), PhDph2 cleaves the Cmethyl-S bond, forming 5′-deoxy-5′-(3-aminopropylthio) adenosine (dAPTA, 1). The methyl cleavage activity, like the cleavage of the other two C-S bonds, is dependent on the presence of a [4Fe-4S]+ cluster. Electron-nuclear double resonance and mass spectroscopy data suggests that mechanistically one of the S atoms in the [4Fe-4S] cluster captures the methyl group from dc-SAM, forming a distinct EPR-active intermediate, which can transfer the methyl group to nucleophiles such as dithiothreitol. This reveals the [4Fe-4S] cluster in a radical SAM enzyme can be tuned to cleave any one of the three bonds to the sulfonium sulfur of SAM or analogues, and is the first demonstration a radical SAM enzyme could switch from an Fe-based one electron transfer reaction to a S-based two electron transfer reaction in a substrate-dependent manner. This study provides an illustration of the versatile reactivity of Fe-S clusters.

SAH derived potent and selective EZH2 inhibitors

A series of novel enhancer of zeste homolog 2 (EZH2) inhibitors was designed based on the chemical structure of the histone methyltransferase (HMT) inhibitor SAH (S-adenosyl-l-homocysteine). These nucleoside-based EZH2 inhibitors blocked the methylation of nucleosomes at H3K27 in biochemical assays employing both WT PRC2 complex as well as a Y641N mutant PRC2 complex. The most potent compound, 27, displayed IC50's against both complexes of 270 nM and 70 nM, respectively. To our knowledge, compound 27 is the most potent SAH-derived inhibitor of the EZH2 PRC2 complex yet identified. This compound also displayed improved potency, lipophilic efficiency (LipE), and selectivity profile against other lysine methyltransferases compared with SAH.

Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L

Histone3-lysine79 (H3K79) methyltransferase DOT1L has been found to be a drug target for acute leukemia with MLL (mixed lineage leukemia) gene translocations. A total of 55 adenosine-containing compounds were designed and synthesized, among which several potent DOT1L inhibitors were identified with Ki values as low as 0.5 nM. These compounds also show high selectivity (>4500-fold) over three other histone methyltransferases. Structure-activity relationships (SAR) of these compounds for their inhibitory activities against DOT1L are discussed. Potent DOT1L inhibitors exhibit selective activity against the proliferation of MLL-translocated leukemia cell lines MV4;11 and THP1 with EC50 values of 4-11 μM. Isothermal titration calorimetry studies showed that two representative inhibitors bind with a high affinity to the DOT1L:nucleosome complex and only compete with the enzyme cofactor SAM (S-adenosyl-l-methionine) but not the substrate nucleosome.

Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors

Potent SAH analogues with constrained homocysteine units have been designed and synthesized as inhibitors of human DNMT enzymes. The five membered (2S,4S)-4-mercaptopyrrolidine-2-carboxylic acid, in 1a, was a good replacement for homocysteine, while the corresponding six-member counterpart was less active. Further optimization of 1a, changed the selectivity profile of these inhibitors. A Chloro substituent at the 2-position of 1a, compound 1d, retained potency against DNMT1, while N6 alkylation, compound 7a, conserved DNMT3b2 activity. The concomitant substitutions of 1a at both 2- and N6 positions reduced activity against both enzymes.

Synthesis and Biochemical Properties of Chemically Stable Product Analogues of the Reaction Catalyzed by S-Adenosyl-L-methionine Decarboxylase

Structural analogues of decarboxylated S-adenosyl-L-methionine (dc-SAM), product of the reaction catalyzed by S-adenosyl-L-methionine decarboxylase (SAM-DC), with modifications in the side-chain portion of the molecule have been synthesized, and their ability to inhibit SAM-DC has been investigated.Mainly, compounds with a nitrogen atom in place of the sulfur were investigated.The data from these inhibition studies have resulted in a delineation of the structural features required for binding on SAM-DC.It was concluded that a terminal primary amino group, a terminal carboxyl group, and the sulfonium functionality are not required for binding on SAM-DC.It was also found that analogues of dc-SAM in which replacement of the sulfur by nitrogen was the only modification were still able to form an azomethine with the enzyme.As found for SAM and dc-SAM, these compounds also caused a time-dependent inactivation of SAM-DC.