The RAG1 and RAG2 proteins are required to assemble mature Ag receptor genes in developing lymphocytes. Hypomorphic mutations in the gene encoding RAG1 are associated with Omenn syndrome, a primary immunodeficiency. We explored the biochemical defects resulting from a mutation identified in an Omenn syndrome patient which generates an amino acid substitution in the RAG1 RING finger/ubiquitin li...

A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and disp...

Several properties of the colchicine-tubulin interaction such as association rate, reversibility, and the promotion of drug fluorescence have been related to the B ring of colchicine. The B ring itself retards the binding rate, and substitution at C-7 leads to further binding rate decreases that appear to be related to both substituent bulk and the presence of a N-acyl group. Thus, the decreasi...

Electrophilic aromatic substitution (EAS) represents one of the most important classes of reactions in all of chemistry. One of the "iron laws" of EAS is that an electron-rich aromatic ring will react more rapidly than an electron-poor ring with suitable electrophiles. In this report, we present unique examples of electron-deficient arenes instead undergoing preferential substitution in intramo...

Possible applications of thiophenes in radiopharmaceutical chemistry have been explored. Thiophene for benzene ring substitution was applied to the synthesis of thienyl-[18F]GBR 13119, an analog of the potent and selective dopamine uptake inhibitor [18F]GBR 13119. In vivo regional brain distribution in mice shows essentially identical results for the thienyl and phenyl compounds (striatum/cereb...

The isomerization of tristriazolotriazione with tangential substituents to radial isomers occurs in a cascade three ring opening/rotation/ring closure steps the central triazine. Donor substitution accelerates which can be catalyzed by Brønsted acids. velocity rearrangements drops each step factor 4, whereas gain heat formation increases. Density functional theory (DFT) calculations led transit...

We present the first large-scale English “allwords lexical substitution” corpus. The size of the corpus provides a rich resource for investigations into word meaning. We investigate the nature of lexical substitute sets, comparing them to WordNet synsets. We find them to be consistent with, but more fine-grained than, synsets. We also identify significant differences to results for paraphrase r...

In this research work, we report the synthesis of macrocyclic diamides from the reaction of diesters and aliphatic diamines in the presence of caesium carbonate. It has been demonstrated that among the carbonate of alkali metals (Li2CO3, Na2CO3, K2CO3 and CS2CO3), CS2CO3 appear to be the best catalyst for macrocyclization. Diesters with different substitution patterns on the aromatic ring react...

nitro-containing heteroaromatic derivatives structurally related to nitroimidazole (metronidazole) are being extensively evaluated against helicobacter pylori isolates. on the other hand, 1,3,4-thiadiazole derivatives have also demonstrated promising antibacterial potential. in present study, we evaluated anti-h. pylori activity of novel hybrid molecules bearing nitroaryl and 1,3,4-thiadiazole ...