Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is proposed that proteins might activate specific atomic positions within bound substrates or co-factors by means of hydrogen-bond chains. As a result of a concerted proton (tautomeric) shift in the linked residues of the hydrogen-bond chain, which includes the bound molecule, a charge separation occurs. The charge thus generated at a specific atom of the bound molecule renders it nucleophilic or electrophilic, as the case may be, and hence 'activated' towards subsequent chemical events. To test the feasibility of the theory a survey of published X-ray diffraction determined structures was performed. A search was made for hydrogen-bond chains which emanate away from bound substrates, co-factors or metal ions in order to validate the existence of such structural arrangements. Secondly, an attempt was made to incorporate the proposed proton dynamics into the proteins' mechanisms of action. Examples in which these criteria were satisfied are carboxypeptidase A, carbonic anhydrase, haemoglobin, dihydrofolate reductase, glutathione reductase and p-hydroxybenzoate hydroxylase.
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PMID:Charge redistribution in proteins via linear hydrogen-bond chains. 309 99

Supramolecular nanomaterials responsive to specific intracellular proteins should be greatly promising for protein sensing and imaging, controlled drug release or dynamic regulation of cellular processes. However, valid design strategies to create useful probes are poorly developed, particularly for proteins inside living cells as targets. We recently reported a unique supramolecular strategy for specific protein detection using self-assembling fluorescent probes consisting of a protein ligand and a fluorophore on the live cell surface, as well as in test tube settings. Herein, we discovered that our self-assembled supramolecular probes having a rhodamine derivative (tetramethylrhodamine or rhodamine-green) can incorporate and stay as less-fluorescent aggregates inside the living cells, so as to sense the protein activity in a reversible manner. Using the overexpressed model protein (dihydrofolate reductase), we demonstrated that this turn-on/off mode is controlled by selective ligand-protein recognition inside the live cells. Not only such a model protein, but also endogenous human carbonic anhydrase and heat shock protein 90 were specifically visualized in living mammalian cells, by use of the similar ligand-tethered supramolecular probes. Furthermore, such reversibility allowed us to intracellularly construct a unique system to evaluate the inhibitors affinity toward specific endogenous proteins in live cells, highlighting the potential of dynamic supramolecules as novel intelligent biomaterials.
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PMID:Intracellular protein-responsive supramolecules: protein sensing and in-cell construction of inhibitor assay system. 2536 66

This review describes research conducted in Thailand from 2000 to 2013 on the discovery of new compounds from local flora and fauna, including those of marine organisms from coastal regions, which have antiplasmodial activity against Plasmodium falciparum growth in culture. These antiplasmodials comprised alkaloids, angucyclinones, anthraquinones, azaanthraquinone, azaphilones, ben- zoquinones, bioxanthracenes, carbazomycins, chalcones, chromone, clerodane, coumarins, cyclomarin, cyclopeptides, cytochalasins, depsidones, depudecin, flavaglines, flavonoids, furans, isoflavonoid limonoids, macrolides, nucleoside, oxepin, peptides, phloroglucinol, polylactone, polypropionate, preussomerins, prodigiosin, pterocarpans, pyrenocines, pyridones, pyrrolidines, quassinoids, quinone, stilbenes, styryl lactones, terpenoids, tetramic acids, tetronic acids, tri- norcadalenes, tropolones, xanthones, and a variety of miscellaneous molecules (a total of 293 compounds). The review also describes the screening and synthesis of novel chemicals targeted against parasite enzymes, (carbonic anhydrase, cy- tochrome bcl, dihydrofolate reductase and orotidine 5'-monophosphate decar- boxylase), which have the potential of being developed into antimalarial drugs. Possible future trends in antimalarial drug research in Thailand are discussed. This review describes research conducted in Thailand from 2000 to 2013
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PMID:Discovery and development of antiplasmodial compounds in Thailand during the 21st century. 2542 44