Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Thiol-ene Enabled Chemical Synthesis of Truncated S-Lipidated Teixobactin Analogs.

ABSTRACT: Herein is described the introduction of lipid moieties onto a simplified teixobactin pharmacophore using a modified Cysteine Lipidation on a Peptide or Amino acid (CLipPA) technique, whereby cysteine was substituted for 3-mercaptopropionic acid (3-MPA). A truncated teixobactin analog was prepared with the requisite thiol handle, thus enabling an array of vinyl esters to be conveniently conjugated onto the simplified teixobactin pharmacophore to yield S-lipidated cyclic lipopeptides.

SUBMITTER: Yim VV

PROVIDER: S-EPMC7417771 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Thiol-ene Enabled Chemical Synthesis of Truncated <i>S</i>-Lipidated Teixobactin Analogs.

Yim Victor V VV Cameron Alan J AJ Kavianinia Iman I Harris Paul W R PWR Brimble Margaret A MA

Frontiers in chemistry 20200804

Herein is described the introduction of lipid moieties onto a simplified teixobactin pharmacophore using a modified Cysteine Lipidation on a Peptide or Amino acid (CLipPA) technique, whereby cysteine was substituted for 3-mercaptopropionic acid (3-MPA). A truncated teixobactin analog was prepared with the requisite thiol handle, thus enabling an array of vinyl esters to be conveniently conjugated onto the simplified teixobactin pharmacophore to yield <i>S</i>-lipidated cyclic lipopeptides. ...[more]

PMID: 32850619

Similar Datasets

Thiol-ene enabled detection of thiophosphorylated kinase substrates.

Project description:Protein phosphorylation is a ubiquitous posttranslational modification that regulates cell signaling in both prokaryotes and eukaryotes. Although the study of phosphorylation has made great progress, several major hurdles remain, including the difficulty of the assignment of endogenous substrates to a discrete kinase and of global phosphoproteomics investigations. We have developed a novel chemical strategy for detecting phosphorylated proteins. This method utilizes adenosine 5'-O-(3-thiotriphosphate) (ATP?S), which results in the transfer of a thiophosphate moiety by a kinase to its substrate(s). This group can subsequently be employed as a nucleophilic handle to promote protein detection. To selectively label thiophosphorylated proteins, cellular thiols (e.g., cysteine-containing proteins) must first be blocked. Most common cysteine-capping strategies rely upon the nucleophilicity of the sulfur group and would therefore also modify the thiophosphate moiety. We hypothesized that the radical-mediated thiol-ene reaction, however, would be selective for cysteine over thiophosphorylated amino acids due to the differences in the electronics and pKa values between these groups. Here, we report rapid and specific tagging of thiophosphorylated proteins in vitro following chemoselective thiol capping using the thiol-ene reaction.

| S-EPMC3745782 | biostudies-literature

Shotgun Analysis of Diacylglycerols Enabled by Thiol-ene Click Chemistry.

Project description:Diacylglycerols (DAGs) are a subclass of neutral lipids actively involved in cell signaling and metabolism. Alteration in DAG metabolism has been associated with onset and progression of several human-related diseases. The structural diversity of DAGs and their low concentrations in biological samples call for the development of methods that are capable of sensitive identification and quantitation of each DAG species as well as rapid profiling when a biochemical pathway is perturbed. In this work, the thiol-ene click chemistry has been employed to introduce a charge-tag, namely, cysteamine (CA), at a carbon-carbon double bond (C═C) of unsaturated DAGs. This one-pot photochemical derivatization is fast (within 1 min), universal (monotagging) for DAGs varying in fatty acyl chain lengths and the number of C═Cs, and suitable for small sample volume (e.g., 1-50 μL plasma). Because of the presence of the amine group in CA, tagged DAGs showed at least 10 times increase in response to electrospray ionization as compared to conventional ammonium adduct formation. Low-energy collision-induced dissociation of CA tagged DAGs allowed confident assignment of fatty acyl composition. A neutral loss scan based on characteristic 95 Da loss (a combined loss of CA and H2O) of tagged DAGs has been established as a sensitive means for unsaturated DAG detection (limit of detection = 100 pM) and quantitation from mixtures. The analytical utility of CA tagging was demonstrated by shotgun analysis of unsaturated DAGs in human plasma, including samples from type 2 diabetes mellitus patients.

| S-EPMC5960015 | biostudies-literature

Synthesis of cyclic, multivalent Arg-Gly-Asp using sequential thiol-ene/thiol-yne photoreactions.

Project description:A unique method has been developed for the formation of multivalent cyclic peptides. This procedure exploits on-resin peptide cyclization using a photoinitiated thiol-ene click reaction and subsequent clustering using thiol-yne photochemistry. Both reactions utilize the sulfhydryl group on natural cysteine amino acids to participate in the thiol-mediated reactions.

| S-EPMC3961633 | biostudies-literature

Surface Chemical Functionalization of Wrinkled Thiol-ene Elastomers for Promoting Cellular Alignment.

Project description:Wrinkled polymer surfaces find broad applicability; however, the polymer substrates are often limited to poly(dimethylsiloxane) (PDMS), which limits spatial control over wrinkle features and surface chemistry. An approach to surface functionalization of wrinkled elastomer substrates is demonstrated through versatile, multistep thiol-ene click chemistry. The elastomer is formed using a thiol-Michael reaction of tetrathiol with excess diacrylates while wrinkle formation is induced through a second free radical UV polymerization of the acrylates on the surface of the elastomer. Due to oxygen inhibition of the free radical polymerization, pendant acrylates at the surface remain unreacted and are subsequently functionalized with a multi-functional thiol, which can be further reacted through a number of thiol-X 'click' reactions. As a demonstration, these thiol surfaces are further modified to either promote cell adhesion of human mesenchymal stem cells (hMSCs) through coupling with RGDS-containing peptides or surface passivation through reaction with hydrophilic hydroxyl ethyl acrylate moieties. Through engineering a combination of surface chemistry and surface topography, hMSCs exhibited increased spreading and cell density on RGDS-functionalized surfaces and a two-fold increase in cell alignment when cultured on wrinkled substrates. Gradient functionalized surfaces created by tuning the wrinkle wavelength with UV irradiation enabled rapid screening of the effect of topography on the hMSCs. Further, this novel application of click chemistry enables simultaneous tuning of wrinkle topology and surface chemistry towards targeted material applications.

| S-EPMC8315696 | biostudies-literature

Total synthesis of teixobactin.

Project description:To cope with the global bacterial multidrug resistance, scientific communities have devoted significant efforts to develop novel antibiotics, particularly those with new modes of actions. Teixobactin, recently isolated from uncultured bacteria, is considered as a promising first-in-class drug candidate for clinical development. Herein, we report its total synthesis by a highly convergent Ser ligation approach and this strategy allows us to prepare several analogues of the natural product.

| S-EPMC4976201 | biostudies-literature

Coaxial PCL/PEG-thiol-ene microfiber with tunable physico-chemical properties for regenerative scaffolds.

Project description:Tissue regeneration requires scaffolds that exhibit mechanical properties similar to the tissues to be replaced while allowing cell infiltration and extracellular matrix production. Ideally, the scaffolds' porous architecture and physico-chemical properties can be precisely defined to address regenerative needs. We thus developed techniques to produce hybrid fibers coaxially structured with a polycaprolactone core and a 4-arm, polyethylene glycol thiol-norbornene sheath. We assessed the respective effects of crosslink density and sheath polymer size on the scaffold architecture, physical and mechanical properties, as well as cell-scaffold interactions in vitro and in vivo. All scaffolds displayed high elasticity, swelling and strength, mimicking soft tissue properties. Importantly, the thiol-ene hydrogel sheath enabled tunable softness and peptide tethering for cellular activities. With increased photopolymerization, stiffening and reduced swelling of scaffolds were found due to intra- and inter-fiber crosslinking. More polymerized scaffolds also enhanced the cell-scaffold interaction in vitro and induced spontaneous, deep cell infiltration to produce collagen and elastin for tissue regeneration in vivo. The molecular weight of sheath polymer provides an additional mechanism to alter the physical properties and biological activities of scaffolds. Overall, these robust scaffolds with tunable elasticity and regenerative cues offered a versatile and effective platform for tissue regeneration.

| S-EPMC6702085 | biostudies-literature

Stereoselective Synthesis of Carbon-Sulfur-Bridged Glycomimetics by Photoinitiated Thiol-Ene Coupling Reactions.

Project description:Oligosaccharides and glycoconjugates are abundant in all living organisms, taking part in a multitude of biological processes. The application of natural O-glycosides in biological studies and drug development is limited by their sensitivity to enzymatic hydrolysis. This issue made it necessary to design hydrolytically stable carbohydrate mimetics, where sulfur, carbon, or longer interglycosidic connections comprising two or three atoms replace the glycosidic oxygen. However, the formation of the interglycosidic linkages between the sugar residues in high diastereoslectivity poses a major challenge. Here, we report on stereoselective synthesis of carbon-sulfur-bridged disaccharide mimetics by the free radical addition of carbohydrate thiols onto the exo-cyclic double bond of unsaturated sugars. A systematic study on UV-light initiated radical mediated hydrothiolation reactions of enoses bearing an exocyclic double bond at C1, C2, C3, C4, C5, and C6 positions of the pyranosyl ring with various sugar thiols was performed. The effect of temperature and structural variations of the alkenes and thiols on the efficacy and stereoselectivity of the reactions was systematically studied and optimized. The reactions proceeded with high efficacy and, in most cases, with complete diastereoselectivity producing a broad array of disaccharide mimetics coupling through an equatorially oriented methylensulfide bridge.

| S-EPMC7013897 | biostudies-literature

Synthesis of non-linear protein dimers through a genetically encoded Thiol-ene reaction.

Project description:Site-specific incorporation of bioorthogonal unnatural amino acids into proteins provides a useful tool for the installation of specific functionalities that will allow for the labeling of proteins with virtually any probe. We demonstrate the genetic encoding of a set of alkene lysines using the orthogonal PylRS/PylTCUA pair in Escherichia coli. The installed double bond functionality was then applied in a photoinitiated thiol-ene reaction of the protein with a fluorescent thiol-bearing probe, as well as a cysteine residue of a second protein, showing the applicability of this approach in the formation of heterogeneous non-linear fused proteins.

| S-EPMC4152134 | biostudies-literature

Thiol-ene/oxidation tandem reaction under visible light photocatalysis: synthesis of alkyl sulfoxides.

Project description:The photocatalyzed synthesis of sulfoxides from alkenes and thiols has been carried out using Eosin Y. This is a metal-free method which uses a low catalyst loading, atmospheric oxygen as the oxidant, and visible light conditions (green light). A mechanism has been proposed that is consistent with the experimental results.

| S-EPMC5779077 | biostudies-literature

Concise Total Synthesis of Lundurines A-C Enabled by Gold Catalysis and a Homodienyl Retro-Ene/Ene Isomerization.

Project description:The total synthesis of lundurines A-C has been accomplished in racemic and enantiopure forms in 11-13 and 12-14 steps, respectively, without protection/deprotection of functional groups, by a novel tandem double condensation/Claisen rearrangement, a gold(I)-catalyzed alkyne hydroarylation, a cyclopropanation via formal [3 + 2] cycloaddition/nitrogen extrusion, and a remarkable olefin migration through a vinylcyclopropane retro-ene/ene reaction that streamlines the endgame.

| S-EPMC4819460 | 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