Ecology
Paul Pumpens in Single-Stranded RNA Phages, 2020
Furthermore, a thorough alkylation analysis was performed on the phage R17 with two groups of alkylating agents: (i) methyl methanesulfonate and dimethyl sulfate and (ii) N-methyl-N-nitrosourea and N-methyl-N′-nitro-N-nitrosoguanidine (Shooter 1974b). The extent of biological inactivation by these alkylating agents was explained by the breaks in the RNA chain, which resulted from hydrolysis of phosphotriesters formed in the alkylation reactions and the rate of hydrolysis increased rapidly as the pH was raised (Shooter et al. 1974a). The mechanism of the biological inactivation of the phage R17 by ethyl methanesulfonate and N-ethyl-N-nitrosourea was unveiled (Shooter and Howse 1975). Then, a group of eight alkylating agents was involved in the R17 studies (Shooter 1975) and acetoxy-dimethylnitrosamine was tested (Shooter and Wiessler 1976).
Molecular Recognition and Chemical Modification of Biopolymers — Two Main Components of Affinity Modification
Dmitri G. Knorre, Valentin V. Vlassov in Affinity Modification of Biopolymers, 1989
Another typical example of damage-selection approach application is the investigation of contacts between E. coli RNA polymerase and the early A3 promoter of phage T7.86 RNA polymerase was complexed to the promoter fragment modified at phosphodiester bonds with ethylnitrosourea. The fragments bearing phosphotriesters at positions that interfere with the complex formation could be separated from the others complexed to the enzyme by filtration through nitrocellulose which traps the protein-DNA complex. The filtrate contained only those promoter molecules modified at positions which prevent polymerase binding. A determination of positions of alkylted phosphates in the DNA fragment from the filtrate has revealed the phosphates whose modification interfered with the enzyme binding. The same experimental procedure was used for identifying purines essential for RNA polymerase binding. Alkylation with dimethyl sulfate was used in this case. These modification-interference experiments pinpointed phosphates of the DNA backbone and purines directly interacting or closely juxtaposed with the polymerase. Together with experiments on the protection by the enzyme of DNA purines from alkylation with dimethyl sulfate, these experiments identified regions crucial for both polymerase recognition and binding: the Pribnow Box and −35 region (Figure 16).
Other Reactions from Gloves
Robert N. Phalen, Howard I. Maibach in Protective Gloves for Occupational Use, 2023
Pyrethroid insecticides (cypermethrin and beta-cyfluthrin) from an insect sprayer were reported to have caused chemical leukoderma on the head, trunk, and extremities of a patient who worked for 15 years spraying insecticides.94 Hexamethylenetetramine, a chemical found in adhesives and sealants, was reported to cause chemical leukoderma in a factory worker who mixed adhesives, chemicals, and other raw materials together to produce automobile materials.95 In China, two cases of chemical leukoderma due to dimethyl sulfate, a chemical used in the production of pharmaceuticals, perfumes, and pesticides, were recently described.96
Synthetic lethality on drug discovery: an update on cancer therapy
Published in Expert Opinion on Drug Discovery, 2020
M. Shahar Yar, Kashif Haider, Vivek Gohel, Nasir Ali Siddiqui, Ahmed Kamal
In the perspective of the treatment of cancer, PARP inhibitors originally proposed as chemosensitizers; PARP 1 has a well-defined role in DNA repair, and the PARP 1-deficient cells especially responsive to certain injure DNA compounds. In the early 1980s, 3-aminobenzamide shown to enhance the cytotoxic effects of DNA methylating agent of dimethyl sulfate and a variety of preclinical studies have shown that PARP inhibitors enhance the effects of temozolomide, another DNA methylating agent. The findings led to the clinical judgment of the PARP inhibitor along with temozolomide, with encouraging results in individuals with metastatic melanoma. Inhibition of PARP can amplify the effects of agents such as temozolomide by inhibiting base excision repair proteins, the main path to repair some DNA lesions produced by methylating agent. Additional combination therapies has also been suggested, especially PARP inhibitors with either radiotherapy or topoisomerase I inhibitor [32] and clinical trials examined the PARP inhibitor combination therapy with carboplatin, dacarbizine, irinotecan, topotecan or radiotherapy with temozolomide is ongoing. FDA approved PARP inhibitors include drugs niraparib (ovarian cancer), rucaparib (ovarian cancer), olaparib (prostate/ovarian/breast cancer), and drug in Phase 4 talazoparib (EMBRACA) [19] (Figure 4).
Strategies for targeting RNA with small molecule drugs
Published in Expert Opinion on Drug Discovery, 2023
Christopher L. Haga, Donald G. Phinney
To overcome limitations of enzyme-based RNA footprinting, chemical modifiers of solvent-accessible nucleobases were adopted to probe RNA secondary structures. Perhaps the most well-established reagent is dimethyl sulfate (DMS), a compound that alkylates the N-7 cyclic amine of unpaired guanosine residues, which following reduction and cleavage by analine treatment may be detected by PAGE analysis [21]. DMS has also been shown to alkylate the N1 and N3 positions of unpaired adenine and cytosine, respectively [22]. Since these modifications result in early termination of cDNA elongation, their location can be probed by primer extension using reverse transcriptase. Combining this approach with RNA sequencing permits massively multiplexed RNA secondary structural determination on the level of the entire RNA transcriptome (DMS-Seq and DMS-MaPseq) [23,24]. Because DMS is a small molecule capable of permeating cell membranes, probing RNA secondary structures in cellulo is also possible.
Preparation and Evaluation of N-Trimethyl Chitosan Nanoparticles of Flurbiprofen for Ocular Delivery
Published in Current Eye Research, 2019
Ujwala A. Shinde, Prajakta N. Joshi, Divya D. Jain, Kavita Singh
TMC was synthesized by the method reported by Britto et al.12 Briefly, a suspension of CS (1 g) was prepared in a mixture of dimethyl sulfate (16 mL) and distilled water (4 mL). To this 0.03 M NaOH and 0.015 M NaCl were added and the solution was mixed under magnetic stirring for 15 min followed by refluxing at 70°C. The derivative so obtained was purified by dialysis through cellophane membrane (cut-off 12,000–14,000 g mol) against distilled water for three days followed by lyophilization to obtain the final product. The yield of TMC was optimized by changing the process variables, time and temperature.
Related Knowledge Centers
- Alkylation
- Chemical Compound
- Ester
- Methanol
- Methyl Group
- Sulfate
- Sulfuric Acid
- Toxicity
- Chemical Formula
- Methyl Trifluoromethanesulfonate