Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of c-di-GMP analogs with thiourea, urea, carbodiimide, and guanidinium linkages.

ABSTRACT: The first syntheses of neutral thiourea, urea, and carbodiimide analogs, along with two guanidinium analogs, of the bacterial signaling molecule cyclic diguanosine monophosphate (c-di-GMP) are reported. The key intermediate, obtained in nine steps, is a 3'-amino-5'-azido-3',5'-dideoxy derivative. The 5'-azide serves as a masked amine from which the amine is obtained by Staudinger reduction, while the 3'-amine is converted to an isothiocyanate that, while stable to chromatography, and Staudinger conditions, nevertheless reacts well with the 5'-amine.

SUBMITTER: Gaffney BL

PROVIDER: S-EPMC3933394 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of c-di-GMP analogs with thiourea, urea, carbodiimide, and guanidinium linkages.

Gaffney Barbara L BL Jones Roger A RA

Organic letters 20131206 1

The first syntheses of neutral thiourea, urea, and carbodiimide analogs, along with two guanidinium analogs, of the bacterial signaling molecule cyclic diguanosine monophosphate (c-di-GMP) are reported. The key intermediate, obtained in nine steps, is a 3'-amino-5'-azido-3',5'-dideoxy derivative. The 5'-azide serves as a masked amine from which the amine is obtained by Staudinger reduction, while the 3'-amine is converted to an isothiocyanate that, while stable to chromatography, and Staudinger ...[more]

PMID: 24313312

Similar Datasets

Synthesis and Leishmanicidal Activity of Novel Urea, Thiourea, and Selenourea Derivatives of Diselenides.

Project description:A novel series of thirty-one N-substituted urea, thiourea, and selenourea derivatives containing diphenyldiselenide entities were synthesized, fully characterized by spectroscopic and analytical methods, and screened for their in vitro leishmanicidal activities. The cytotoxic activity of these derivatives was tested against Leishmania infantum axenic amastigotes, and selectivity was assessed in human THP-1 cells. Thirteen of the synthesized compounds showed a significant antileishmanial activity, with 50% effective concentration (EC50) values lower than that for the reference drug miltefosine (EC50, 2.84 μM). In addition, the derivatives 9, 11, 42, and 47, with EC50 between 1.1 and 1.95 μM, also displayed excellent selectivity (selectivity index ranged from 12.4 to 22.7) and were tested against infected macrophages. Compound 11, a derivative with a cyclohexyl chain, exhibited the highest activity against intracellular amastigotes, with EC50 values similar to those observed for the standard drug edelfosine. Structure-activity relationship analyses revealed that N-aliphatic substitution in urea and selenourea is recommended for the leishmanicidal activity of these analogs. Preliminary studies of the mechanism of action for the hit compounds was carried out by measuring their ability to inhibit trypanothione reductase. Even though the obtained results suggest that this enzyme is not the target for most of these derivatives, their activity comparable to that of the standards and lack of toxicity in THP-1 cells highlight the potential of these compounds to be optimized for leishmaniasis treatment.

| S-EPMC6496061 | biostudies-literature

Synthesis of biotinylated c-di-gmp and c-di-amp using click conjugation.

Project description:The biotinylated c-di-GMP and c-di-AMP conjugates 10a/b were synthesized by a straightforward set of procedures from standard, commercially available phosphoramidites. Their availability should allow isolation and characterization of new protein and RNA receptors for these key bacterial signaling molecules.

| S-EPMC3561633 | biostudies-literature

Vibrio vulnificus: normal intracellular c-di-GMP level vs. high intracellular c-di-GMP level

Project description:The profiles of transcripts from the V. vulnificus grown under normal and high c-di-GMP conditions were compared by using a V. vulnificus whole-genome microarray Two-condition experiment, normal c-di-GMP condition vs. high c-di-GMP condition. Biological replicates: 3 control, 3 experimental, independently grown and harvested. One replicate per array. For transcriptome analysis, the V. vulnificus whole genome TwinChip, manufactured and kindly provided by the 21C Frontier Microbial Genomics and Applications Center (Daejeon, South Korea), was used.

2013-10-22 | E-GEOD-51459 | biostudies-arrayexpress

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea.

Project description:The three-component reactions of aldehydes, electron deficient alkynes and ureas/thioureas have been smoothly performed to yield a class of unprecedented 3,4-dihydropyrimidinones and thiones (DHPMs). The reactions are initiated by the key transformation of an enamine-type activation involving the addition of a secondary amine to an alkyne, which enables the subsequent incorporation of aldehydes and ureas/thioureas. This protocol tolerates a broad range of aryl- or alkylaldehydes, N-substituted and unsubstituted ureas/thioureas and alkynes to yield the corresponding DHPMs with specific regioselectivity.

| S-EPMC3943560 | biostudies-literature

Vibrio vulnificus: normal intracellular c-di-GMP level vs. high intracellular c-di-GMP level

Project description:The profiles of transcripts from the V. vulnificus grown under normal and high c-di-GMP conditions were compared by using a V. vulnificus whole-genome microarray

2013-10-22 | GSE51459 | GEO

Allosteric activation of exopolysaccharide synthesis through cyclic di-GMP-stimulated protein-protein interaction.

Project description:In many bacterial pathogens, the second messenger c-di-GMP stimulates the production of an exopolysaccharide (EPS) matrix to shield bacteria from assaults of the immune system. How c-di-GMP induces EPS biogenesis is largely unknown. Here, we show that c-di-GMP allosterically activates the synthesis of poly-?-1,6-N-acetylglucosamine (poly-GlcNAc), a major extracellular matrix component of Escherichia coli biofilms. C-di-GMP binds directly to both PgaC and PgaD, the two inner membrane components of the poly-GlcNAc synthesis machinery to stimulate their glycosyltransferase activity. We demonstrate that the PgaCD machinery is a novel type c-di-GMP receptor, where ligand binding to two proteins stabilizes their interaction and promotes enzyme activity. This is the first example of a c-di-GMP-mediated process that relies on protein-protein interaction. At low c-di-GMP concentrations, PgaD fails to interact with PgaC and is rapidly degraded. Thus, when cells experience a c-di-GMP trough, PgaD turnover facilitates the irreversible inactivation of the Pga machinery, thereby temporarily uncoupling it from c-di-GMP signalling. These data uncover a mechanism of c-di-GMP-mediated EPS control and provide a frame for c-di-GMP signalling specificity in pathogenic bacteria.

| S-EPMC3567491 | biostudies-literature

Recent advances in urea- and thiourea-containing compounds: focus on innovative approaches in medicinal chemistry and organic synthesis.

Project description:Urea and thiourea represent privileged structures in medicinal chemistry. Indeed, these moieties constitute a common framework of a variety of drugs and bioactive compounds endowed with a broad range of therapeutic and pharmacological properties. Herein, we provide an overview of the state-of-the-art of urea and thiourea-containing pharmaceuticals. We also review the diverse approaches pursued for (thio)urea bioisosteric replacements in medicinal chemistry applications. Finally, representative examples of recent advances in the synthesis of urea- and thiourea-based compounds by enabling chemical tools are discussed.

| S-EPMC8293013 | biostudies-literature

The bacterial second messenger c-di-GMP: probing interactions with protein and RNA binding partners using cyclic dinucleotide analogs.

Project description:The ability of bacteria to adapt to a changing environment is essential for their survival. One mechanism used to facilitate behavioral adaptations is the second messenger signaling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP). c-di-GMP is widespread throughout the bacterial domain and plays a vital role in regulating the transition between the motile planktonic lifestyle and the sessile biofilm forming state. This second messenger also controls the virulence response of pathogenic organisms and is thought to be connected to quorum sensing, the process by which bacteria communicate with each other. The intracellular concentration of c-di-GMP is tightly regulated by the opposing enzymatic activities of diguanlyate cyclases and phosphodiesterases, which synthesize and degrade the second messenger, respectively. The change in the intracellular concentration of c-di-GMP is directly sensed by downstream targets of the second messenger, both protein and RNA, which induce the appropriate phenotypic response. This review will summarize our current state of knowledge of c-di-GMP signaling in bacteria with a focus on protein and RNA binding partners of the second messenger. Efforts towards the synthesis of c-di-GMP and its analogs are discussed as well as studies aimed at targeting these macromolecular effectors with chemically synthesized cyclic dinucleotide analogs.

| S-EPMC3589761 | biostudies-literature

Biofilms and Cyclic di-GMP (c-di-GMP) Signaling: Lessons from Pseudomonas aeruginosa and Other Bacteria.

Project description:The cyclic di-GMP (c-di-GMP) second messenger represents a signaling system that regulates many bacterial behaviors and is of key importance for driving the lifestyle switch between motile loner cells and biofilm formers. This review provides an up-to-date compendium of c-di-GMP pathways connected to biofilm formation, biofilm-associated motilities, and other functionalities in the ubiquitous and opportunistic human pathogen Pseudomonas aeruginosa This bacterium is frequently adopted as a model organism to study bacterial biofilm formation. Importantly, its versatility and adaptation capabilities are linked with a broad range of complex regulatory networks, including a large set of genes involved in c-di-GMP biosynthesis, degradation, and transmission.

| S-EPMC4933438 | biostudies-literature

Signaling specificity in the c-di-GMP-dependent network regulating antibiotic synthesis in Lysobacter.

Project description:Enzymes controlling intracellular second messengers in bacteria, such as c-di-GMP, often affect some but not other targets. How such specificity is achieved is understood only partially. Here, we present a novel mechanism that enables specific c-di-GMP-dependent inhibition of the antifungal antibiotic production. Expression of the biosynthesis operon for Heat-Stable Antifungal Factor, HSAF, in Lysobacter enzymogenes occurs when the transcription activator Clp binds to two upstream sites. At high c-di-GMP levels, Clp binding to the lower-affinity site is compromised, which is sufficient to decrease gene expression. We identified a weak c-di-GMP phosphodiesterase, LchP, that plays a disproportionately high role in HSAF synthesis due to its ability to bind Clp. Further, Clp binding stimulates phosphodiesterase activity of LchP. An observation of a signaling complex formed by a c-di-GMP phosphodiesterase and a c-di-GMP-binding transcription factor lends support to the emerging paradigm that such signaling complexes are common in bacteria, and that bacteria and eukaryotes employ similar solutions to the specificity problem in second messenger-based signaling systems.

| S-EPMC6182147 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data