190774-49-3Relevant academic research and scientific papers
Thiol-yne radical reaction mediated site-specific protein labeling via genetic incorporation of an alkynyl-l-lysine analogue
Li, Yiming,Pan, Man,Li, Yitong,Huang, Yichao,Guo, Qingxiang
, p. 2624 - 2629 (2013)
Three alkyne-containing pyrrolysine derivatives were synthesized and genetically encoded into proteins by a mutant PylRS-tRNA pair with high efficiencies. With these alkyne handles, site-specific dual labeling of proteins can be achieved via a bioorthogonal thiol-yne ligation reaction.
An Activity-Based Probe Targeting Non-Catalytic, Highly Conserved Amino Acid Residues within Bromodomains
D'Ascenzio, Melissa,Pugh, Kathryn M.,Konietzny, Rebecca,Berridge, Georgina,Tallant, Cynthia,Hashem, Shaima,Monteiro, Octovia,Thomas, Jason R.,Schirle, Markus,Knapp, Stefan,Marsden, Brian,Fedorov, Oleg,Bountra, Chas,Kessler, Benedikt M.,Brennan, Paul E.
, p. 1007 - 1012 (2019)
Bromodomain-containing proteins are epigenetic modulators involved in a wide range of cellular processes, from recruitment of transcription factors to pathological disruption of gene regulation and cancer development. Since the druggability of these acetyl-lysine reader domains was established, efforts were made to develop potent and selective inhibitors across the entire family. Here we report the development of a small molecule-based approach to covalently modify recombinant and endogenous bromodomain-containing proteins by targeting a conserved lysine and a tyrosine residue in the variable ZA or BC loops. Moreover, the addition of a reporter tag allowed in-gel visualization and pull-down of the desired bromodomains.
Multiplexed Small-Molecule-Ligand Binding Assays by Affinity Labeling and DNA Sequence Analysis**
Cai, Bo,Krusemark, Casey J.
supporting information, (2021/12/06)
Small-molecule binding assays to target proteins are a core component of drug discovery and development. While a number of assay formats are available, significant drawbacks still remain in cost, sensitivity, and throughput. To improve assays by capitalizing on the power of DNA sequence analysis, we have developed an assay method that combines DNA encoding with split-and-pool sample handling. The approach involves affinity labeling of DNA-linked ligands to a protein target. Critically, the labeling event assesses ligand binding and enables subsequent pooling of several samples. Application of a purifying selection on the pool for protein-labeled DNAs allows detection of ligand binding by quantification of DNA barcodes. We demonstrate the approach in both ligand displacement and direct binding formats and demonstrate its utility in determination of relative ligand affinity, profiling ligand specificity, and high-throughput small-molecule screening.
A Covalent Approach for Site-Specific RNA Labeling in Mammalian Cells
Li, Fahui,Dong, Jianshu,Hu, Xiaosong,Gong, Weimin,Li, Jiasong,Shen, Jing,Tian, Huifang,Wang, Jiangyun
supporting information, p. 4597 - 4602 (2015/04/14)
Advances in RNA research and RNA nanotechnology depend on the ability to manipulate and probe RNA with high precision through chemical approaches, both in vitro and in mammalian cells. However, covalent RNA labeling methods with scope and versatility comp
Base catalyzed cyclization of N-aryl and N-alkyl-O-propargyl carbamates to 4-alkylidene-2-oxazolidinones
Ramesh, Ramapanicker,Chandrasekaran, Yogesh,Megha, Rajendran,Chandrasekaran, Srinivasan
, p. 9153 - 9162 (2008/02/10)
The base catalyzed cyclization of N-aryl and N-alkyl-O-propargyl carbamates is studied in detail. The effect of various bases and solvents on the efficacy of this cyclization reaction is analyzed and a new base-solvent system (LiOH in DMF) for effective cyclization of these carbamates is reported. A number of differentially substituted O-propargyl carbamates were cyclized to the corresponding 2-oxazolidinones under these conditions. The reaction conditions reported here are mild and no side reactions were observed in any of the substrates studied. A propargyl carbonate group was unaffected during the course of the cyclization of the O-propargyl carbamate group. The propargyl carbamates were prepared from the corresponding alkyl or aryl amines and the corresponding propargyl chloroformate, resulting in oxazolidinones diversely substituted at the nitrogen atom. N-Aryl-O-propargyl carbamates cyclized readily to the corresponding oxazolidinones with LiOH in DMF, whereas N-alkyl-O-propargyl carbamates reacted slowly under the same conditions. O-Propargyl carbamates substituted at the 1-position tend to cyclize faster whereas those substituted at 3-position cyclize considerably slower than the unsubstituted carbamates.
Synthesis of substituted α-methylene-γ-butyrolactones from chloroformates via palladium catalysed cyclisation-anion capture
Grigg,Savic
, p. 2381 - 2382 (2007/10/03)
Cyclisation of chloroformates onto proximate alkyne functionality in the presence of a Pd(0) catalyst followed by anion capture affords α-methylene-γ-butyrolactone derivatives in moderate to good yields.
Synthesis of γ- and δ-Lactones by Free-Radical Annelation of Se-Phenyl Selenocarbonates
Bachi, Mario D.,Bosch, Eric
, p. 4696 - 4705 (2007/10/02)
A general method for the synthesis of γ- and δ-lactones through the intramolecular addition of alkoxycarbonyl radicals, formed by reaction of Se-phenylselenocarbonates with n-Bu3SnH, onto carbon-carbon multiple bonds is described.This free-radical cyclization is characterized by high regioselectivity favoring exo addition and by a high ratio of cyclization to reduction.Monocyclic, fused bicyclic, and spirocyclic lactones are formed in good to excellent yield.Use of allyltri-n-butyltin as a chain-transfer agent in the place of n-Bu3SnH affords the corresponding 3-butenyl lactones.
