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1.
Nature ; 616(7956): 288-292, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37045922

RESUMO

Water is one of the most important substances on our planet1. It is ubiquitous in its solid, liquid and vaporous states and all known biological systems depend on its unique chemical and physical properties. Moreover, many materials exist as water adducts, chief among which are crystal hydrates (a specific class of inclusion compound), which usually retain water indefinitely at subambient temperatures2. We describe a porous organic crystal that readily and reversibly adsorbs water into 1-nm-wide channels at more than 55% relative humidity. The water uptake/release is chromogenic, thus providing a convenient visual indication of the hydration state of the crystal over a wide temperature range. The complementary techniques of X-ray diffraction, optical microscopy, differential scanning calorimetry and molecular simulations were used to establish that the nanoconfined water is in a state of flux above -70 °C, thus allowing low-temperature dehydration to occur. We were able to determine the kinetics of dehydration over a wide temperature range, including well below 0 °C which, owing to the presence of atmospheric moisture, is usually challenging to accomplish. This discovery unlocks opportunities for designing materials that capture/release water over a range of temperatures that extend well below the freezing point of bulk water.

2.
Fungal Genet Biol ; 42(4): 328-38, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15749052

RESUMO

Candida albicans genes involved in mating have been identified previously by homology to Saccharomyces cerevisiae mating pathway components. The C. albicans genome encodes CaSte2p, a homolog of the S. cerevisiae alpha-mating pheromone receptor Ste2p, and two potential pheromones, alpha-F13 (GFRLTNFGYFEPG) and alpha-F14 (GFRLTNFGYFEPGK). The response of several C. albicans strains to the synthesized peptides was determined. The alpha-F13 was degraded by a C. albicans MTLa strain but not by S. cerevisiae MATa cells. The CaSTE2 gene was cloned and expressed in a ste2-deleted strain of S. cerevisiae. Growth arrest and beta-galactosidase activity induced from a FUS1-lacZ reporter construct increased in a dose-dependent manner upon exposure of transgenic S. cerevisiae to alpha-F13. Mating between the strain expressing CaSTE2 and an opposite mating type was mediated by alpha-F13 and not by the S. cerevisiae alpha-factor. The results indicated that CaSte2p effectively coupled to the S. cerevisiae signal transduction pathway. Functional expression of CaSte2p in S. cerevisiae provides a well-defined system for studying the biochemistry and molecular biology of the C. albicans pheromone and its receptor.


Assuntos
Candida albicans/metabolismo , Regulação Fúngica da Expressão Gênica , Receptores de Peptídeos/metabolismo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiologia , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Meios de Cultura , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fator de Acasalamento , Peptídeos/síntese química , Peptídeos/química , Peptídeos/metabolismo , Receptores de Fator de Acasalamento , Receptores de Peptídeos/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Transdução de Sinais , Fatores de Transcrição/genética
3.
Bioorg Med Chem ; 11(8): 1653-62, 2003 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-12659751

RESUMO

Several N-acyl and ester derivatives of 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP) have been synthesised and tested as inhibitors of fungal enzymes involved in early steps of chitin biosynthesis and for antifungal activity. All the tested derivatives were found to be much poorer inhibitors of the enzyme, D-glucosamine-6-phosphate (GlcN-6-P) synthase, than the parent compound but some of them exhibited much better antifungal activity. MIC values for the investigated compounds ranged between 10 mg mL(-1), found for ADGP and 0.3 mg mL(-1) for the most active derivative, namely ADGP dimethyl ester. Increased affinity of ADGP derivatives to the artificial immobilised cell membrane was correlated with their enhanced ability to be taken up by fungal cells by free diffusion. It was found that some of the examined derivatives behaved as 'pro-drugs' and after internalisation were converted into ADGP in the cell-free extract. This conversion was relatively rapid for ADGP esters but very slow for N-acyl derivatives. Results of our studies demonstrate a possibility of design and preparation of GlcN-6-P synthase inhibitors exhibiting antifungal activity.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/antagonistas & inibidores , Sorbitol/análogos & derivados , Sorbitol/química , Sorbitol/farmacologia , Fosfatos Açúcares/química , Fosfatos Açúcares/farmacologia , Acilação , Antifúngicos/metabolismo , Candida albicans/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Fungos/efeitos dos fármacos , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Concentração Inibidora 50 , Cinética , Testes de Sensibilidade Microbiana , Sorbitol/síntese química , Sorbitol/metabolismo , Relação Estrutura-Atividade , Fosfatos Açúcares/síntese química , Fosfatos Açúcares/metabolismo
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