7689-60-3

Usage

Chemical Properties

White Solid

Uses

Intermediate in the preparation of L-(+)-Cystathionine.

InChI:InChI=1/C11H15NO2S/c12-10(11(13)14)6-7-15-8-9-4-2-1-3-5-9/h1-5,10H,6-8,12H2,(H,13,14)

Upstream product

• 95277-61-5 (S)-benzyl 4-(methylthio)-1-oxo-1-(phenylamino)butan-2-ylcarbamate 
• 102164-48-7 N-acetyl-S-benzyl-L-homocysteine anilide 
• 63-68-3 L-methionine 
• 100-39-0 benzyl bromide 
• 100-44-7 benzyl chloride 
• 6027-13-0 L-homocysteine 
• 626-72-2 L-homocystine 
• 454-29-5 2-amino-4-mercaptobutyric acid 
• 100610-06-8 S-benzyl-N-acetyl-DL-homocysteine 
• 1017-76-1 S-benzyl homocysteine 

Downstream Products

• 6304-80-9 S-benzyl-N-benzyloxycarbonyl-L-homocysteine 
• 16947-99-2 Boc-Hcy(Bzl) 
• 640272-28-2 C₁₂H₁₇NO₃S 
• 97512-79-3 Hcy(Bzl)-OBzl*HCl 
• 63-68-3 L-methionine 
• 30651-43-5 (2R,2'S)-2-amino-4-(2'-amino-2'-carboxyethylsulfanyl)butanoic acid 
• 142435-77-6 S-benzyl-N-acetyl-L-homocysteine 
• 2338-04-7 L-homocysteine thiolactone 
• 626-72-2 L-homocystine 
• 31982-10-2 L-homolanthionine 
• 13073-21-7 S-butyl-L-homocysteine 
• 13073-35-3 DL-ethionine 
• 6027-13-0 L-homocysteine 

Relevant academic research and scientific papers

Synthesis of non-natural cofactor analogs of S-adenosyl-L-methionine using methionine adenosyltransferase

The present disclosure relates to the synthesis of non-natural analogs of S-adenosyl-L-methionine (SAM) and/or of Se-adenosyl-L-methionine (SeAM) by reacting a methionine analog and adenosine triphosphate (ATP) in the presence of at least one methionine adenosyltransferase (MAT), and to use thereof with downstream SAM and/or SeAM utilizing enzymes. The non-natural analogs of SAM and/or SeAM have the general formula: where X is S or Se, and R1 is an alkyl group.

Facile chemoenzymatic strategies for the synthesis and utilization of S-adenosyl-L-methionine analogues

A chemoenzymatic platform for the synthesis of S-adenosyl-L-methionine (SAM) analogues compatible with downstream SAM-utilizing enzymes is reported. Forty-four non-native S/Se-alkylated Met analogues were synthesized and applied to probing the substrate specificity of five diverse methionine adenosyltransferases (MATs). Human MAT II was among the most permissive of the MATs analyzed and enabled the chemoenzymatic synthesis of 29 non-native SAM analogues. As a proof of concept for the feasibility of natural product alkylrandomization , a small set of differentially-alkylated indolocarbazole analogues was generated by using a coupled hMAT2-RebM system (RebM is the sugar C4′-O-methyltransferase that is involved in rebeccamycin biosynthesis). The ability to couple SAM synthesis and utilization in a single vessel circumvents issues associated with the rapid decomposition of SAM analogues and thereby opens the door for the further interrogation of a wide range of SAM utilizing enzymes. Mix and MATch: Methionine adenosyltransferase (MAT) was used to synthesize S-adenosylmethionine (SAM) analogues in a method directly compatible with downstream SAM-utilizing enzymes. As a proof of concept for the feasibility of natural product alkylrandomization by using this method, a coupled strategy in which MAT was applied in conjunction with the methyltransferase RebM was used to generate a small set of indolocarbazole analogues.

A sensitive mass spectrum assay to characterize engineered methionine adenosyltransferases with S-alkyl methionine analogues as substrates

Methionine adenosyltransferases (MATs) catalyze the formation of S-adenosyl-l-methionine (SAM) inside living cells. Recently, S-alkyl analogues of SAM have been documented as cofactor surrogates to label novel targets of methyltransferases. However, these chemically synthesized SAM analogues are not suitable for cell-based studies because of their poor membrane permeability. This issue was recently addressed under a cellular setting through a chemoenzymatic strategy to process membrane-permeable S-alkyl analogues of methionine (SAAMs) into the SAM analogues with engineered MATs. Here we describe a general sensitive activity assay for engineered MATs by converting the reaction products into S-alkylthioadenosines, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) quantification. With this assay, 40 human MAT mutants were evaluated against 7 SAAMs as potential substrates. The structure-activity relationship revealed that, besides better engaged SAAM binding by the MAT mutants (lower Km value in contrast to native MATs), the gained activity toward the bulky SAAMs stems from their ability to maintain the desired linear SN2 transition state (reflected by higher kcat value). Here the I117A mutant of human MATI was identified as the most active variant for biochemical production of SAM analogues from diverse SAAMs.

Chemoenzymatic synthesis and in situ application of S-adenosyl-l-methionine analogs

Analogs of S-adenosyl-l-methionine (SAM) are increasingly applied to the methyltransferase (MT) catalysed modification of biomolecules including proteins, nucleic acids, and small molecules. However, SAM and its analogs suffer from an inherent instability, and their chemical synthesis is challenged by low yields and difficulties in stereoisomer isolation and inhibition. Here we report the chemoenzymatic synthesis of a series of SAM analogs using wild-type (wt) and point mutants of two recently identified halogenases, SalL and FDAS. Molecular modelling studies are used to guide the rational design of mutants, and the enzymatic conversion of l-Met and other analogs into SAM analogs is demonstrated. We also apply this in situ enzymatic synthesis to the modification of a small peptide substrate by protein arginine methyltransferase 1 (PRMT1). This technique offers an attractive alternative to chemical synthesis and can be applied in situ to overcome stability and activity issues.

Ring size of somatostatin analogues (ODT-8) modulates receptor selectivity and binding affinity

The synthesis, biological testing, and NMR studies of several analogues of H-c[Cys3-Phe6-Phe7-DTrp8-Lys 9-Thr10-Phe11-Cys14]-OH (ODT-8, a pan-somatostatin analogue, 1)

Dealkylation of Quaternary Ammonium Salts by Thiolate Anions: A Model of the Cobalamin-independent Methionine Synthase Reaction.

The reactions of thiolate ions derived from thiophenol and homocysteine with substituted quaternary ammonium salts result in alkyl transfer from nitrogen to sulfur.A radical mechanism for this transalkylation, accounts for the reactivity pattern of the substrate salts.In a model study of the cobalamin-independent methionine synthase reaction, 5,5,6,7-tetramethyl-5,6,7,8-tetrahydropteridinium salt (25), which can be considered as a model for the natural coenzyme 5-CH3H4-folate (1), was allowed to react with the thiolate of homocysteine, whereupon the formation of methionine was observed in good yield.These results suggest that in the enzymatic process the N(5)-CH3 bond may be activated for the methyl transfer step, by coordination of the N(5) with an electrophile or a proton at the active site.

Aldehyde derivatives and their use as calpain inhibitors

Aldehyde derivatives with a specific calpain inhibiting activity and a platelet-aggregation inhibiting effect with formula (I) or formula (II): wherein R1 represents an aromatic hydrocarbon group, a heterocyclic group, or a group of-X-R3 in which X represents O,-S(O)m-(m = 0, 1, or 2), and R3 represents an aromatic hydrocarbon group, a heterocyclic group, or an alkyl group; Z represents R?-Y-or R?O-CH(R?)-in which Y represents a 3-to 7-membered nitrogen-containing saturated heterocyclic group, or a single cyclic saturated hydrocarbon group, R? represents an alkyl group, an alkenyl group, an alkynyl group, an acyl group, a sulfonyl group, an alkoxycarbonyl group, a carbamoyl group, or a thiocarbamoyl group, R? represents hydrogen, an alkyl group, or an aromatic hydrocarbon group, and R? represents an acyl group, a carbamoyl group, a thiocarbamoyl group, or an alkyl group; and n is an integer of 1 to 5. wherein R?, R?, R?, and R1? are defined in the specification.