ChemInform Abstract: 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.

Pignot, Marc; Pljevaljčić, Goran; Weinhold, Elmar G.

doi:10.1002/chin.200016237

Cited by 2 publications

(4 citation statements)

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“…The 5′- S -acetyl-5′-thioadenosine derivatives 9a and 9b were prepared from 2′,3′-isopropylideneadenosine ( 8 ) according to Pignot’s procedure ( 50 ). Reactions of 9a or 9b with 2,2′-dithiobis(5-nitropyridine) in an ammonia-saturated methanol solution at 0°C yielded the corresponding 5′-deoxy-5′-(5-nitropyridinyl-2-disulfanyl)adenosine derivatives ( 10a and b ) in 80 and 85% yields, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…A solution of 5′-acetylthio-5′-deoxy-2′,3′- O -isopropylideneadenosine ( 9a ) ( 50 ) (365 mg, 1.0 mmol) in a mixed solvent of methanol (10 ml) and dichloromethane (5 ml) was saturated with ammonia at 0°C for 30 min. 2,2′-Dithiobis(5-nitropyridine) (620 g, 2.0 mmol) was then added, and the mixture was kept at 4°C for 48 h. The solvent was removed, and the residue was isolated by silica gel chromatography, eluting with 3–5% methanol in chloroform to give 10a (383 mg, 80% yield).…”

Section: Methodsmentioning

confidence: 99%

“…A solution of 5′-acetylthio-5′-deoxyadenosine ( 9b ) ( 50 ) (0.96 g, 2.95 mmol) in methanol (3.0 ml) was saturated with ammonia at 0°C for 1 h and then kept at 0°C for additional 1 h. Thin layer chromatography showed that the reaction was complete. 2,2′-Dithiobis(5-nitropyridine) (1.66 g, 5.35 mmol) was then added, and the mixture was stirred at room temperature for 2 h. The solvent was removed and the residue was isolated by silica gel chromatography, eluting with 5% methanol in chloroform to recover the excess 2,2′-dithiobis(5-nitropyridine), followed by elution with 10% methanol in chloroform to give 10b (1.091 g, 85% yield).…”

Section: Methodsmentioning

confidence: 99%

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A general and efficient approach for the construction of RNA oligonucleotides containing a 5′-phosphorothiolate linkage

Li¹,

Frederiksen²,

Koo³

et al. 2010

Nucleic Acids Research

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Oligoribonucleotides containing a 5′-phosphorothiolate linkage have provided effective tools to study the mechanisms of RNA catalysis, allowing resolution of kinetic ambiguity associated with mechanistic dissection and providing a strategy to establish linkage between catalysis and specific functional groups. However, challenges associated with their synthesis have limited wider application of these modified nucleic acids. Here, we describe a general semisynthetic strategy to obtain these oligoribonucleotides reliably and relatively efficiently. The approach begins with the chemical synthesis of an RNA dinucleotide containing the 5′-phosphorothiolate linkage, with the adjacent 2′-hydroxyl group protected as the photolabile 2′-O-o-nitrobenzyl or 2′-O-α-methyl-o-nitrobenzyl derivative. Enzymatic ligation of the 2′-protected dinucleotide to transcribed or chemically synthesized 5′ and 3′ flanking RNAs yields the full-length oligoribonucleotide. The photolabile protecting group increases the chemical stability of these highly activated oligoribonucleotides during synthesis and long-term storage but is easily removed with UV irradiation under neutral conditions, allowing immediate use of the modified RNA in biochemical experiments.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A general and efficient approach for the construction of RNA oligonucleotides containing a 5′-phosphorothiolate linkage

Li¹,

Frederiksen²,

Koo³

et al. 2010

Nucleic Acids Research

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show abstract

“…Lactonization transition state of AHL synthases. compounds JKR-1, 2, 3, 5 and 7 were all prepared from 5' thioacetyladenosine acetal, prepared by Mitsunobu reaction of protected adenosine and thioacetic acid 27. The 5' thiol was liberated by basic methanolysis and coupled to suitable halides (Scheme 1).…”

mentioning

confidence: 99%

Design, Synthesis, and Evaluation of Transition-State Analogs as Inhibitors of the Bacterial Quorum Sensing Autoinducer Synthase CepI

Higgins¹,

Kellner-Rogers²,

Estanislau³

et al. 2020

Preprint

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Quorum sensing is a bacterial signaling system that involves the synthesis and subsequent detection of signal molecules called autoinducers. The main autoinducer in gram-negative bacteria are acylated homoserine lactones, produced by the LuxI family of autoinducer synthase enzymes and detected by the LuxR family of autoinducer receptors. Quorum sensing allows for changes in gene expression and bacterial behaviors in a coordinated, cell density dependent manner. Quorum sensing controls the expression of virulence factors in some human pathogens, making quorum sensing an antibacterial drug target. Here we describe the design and synthesis of transition-state analogs of the autoinducer synthase enzymatic reaction and the evaluation of these compounds as inhibitors of the synthase CepI. One such compound potently inhibits CepI and constitutes a new type of inhibitor against this underdeveloped antibacterial target.

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ChemInform Abstract: 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.

Cited by 2 publications

References 1 publication

A general and efficient approach for the construction of RNA oligonucleotides containing a 5′-phosphorothiolate linkage

A general and efficient approach for the construction of RNA oligonucleotides containing a 5′-phosphorothiolate linkage

Design, Synthesis, and Evaluation of Transition-State Analogs as Inhibitors of the Bacterial Quorum Sensing Autoinducer Synthase CepI

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