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151.
Mironov A. F. Ruziev R. D. Lebedeva V. S. 《Russian Journal of Bioorganic Chemistry》2004,30(5):466-476
Two series of chlorin p6 13,15-cycloimides that differ in their substituents at the nitrogen atom of the additional six-membered ring were synthesized. The compounds of the first series have a hydroxy, alkoxy, or acyloxy group at the 13,15-cycloimide nitrogen and those of the second series, residues of aliphatic alcohols. The cycloimides synthesized are satisfactorily stable and display an intensive light absorption maximum at 710–718 nm. Treatment of the cycloimides with sodium periodate in the presence of osmium tetroxide and with the Vilsmeier reagent resulted in the formation of 3-formyl- and 3-(2-formylvinyl)derivatives, respectively. The conversion of vinyl into formyl group or 2-formylvinyl group leads to an additional bathochromic shift of the long-wave maximum by 30 nm on average. An extra hydroxy group was introduced at position 18 of the macrocycle to increase the cycloimide hydrophilicity. 相似文献
152.
A. V. Feofanov A. I. Nazarova T. A. Karmakova A. D. Plyutinskaya A. I. Grishin R. I. Yakubovskaya V. S. Lebedeva R. D. Ruziev A. F. Mironov J.-C. Maurizot P. Vigny 《Russian Journal of Bioorganic Chemistry》2004,30(4):374-384
Lipophilic derivatives of chlorin p6, 13,15-N-(carboxymethyl)cycloimide methyl ester (CIC1) and 13,15-N-(2-carboxyethyl)cycloimide methyl ester (CIC2), were shown to absorb light in 710 nm region and to be efficient IR photosensitizers. They exhibit similar phototoxicities on the cells of A549 human lung adenocarcinoma, which are 40- and 100-fold higher than those of chlorin p6 and the clinically used Photogem, respectively, and are not toxic in the absence of light irradiation. The confocal spectral imaging technique allowed us to demonstrate that the high phototoxicity of CIC1 and CIC2 is due to their ability to readily penetrate to cells and to be bound to the cell membranes and lipid-containing structures in the monomeric photoactive form. Under the irradiation, the membrane-bound CIC1 and CIC2 are characterized by high quantum yields of singlet oxygen generation (0.6 and 0.65, respectively) and the inability to produce hydroxyl radicals. A 1.5-M content of CIC1 and CIC2 in the incubation medium provides for their average cytoplasmic concentrations of 21 and 16.5 M, respectively. The incubation times to achieve 50% level of maximum accumulation for CIC1 and CIC2 in A549 cells are 30 ± 6 and 24 ± 12 min, and the times for 50% release of the dyes from the cells are 17 ± 4 and 50 ± 10 min, respectively. A diffuse distribution with the predominant accumulation in the membranes of the Golgi apparatus and mitochondria is characteristic of both CIC2 and CIC1, whereas, in addition, CIC1 is considerably accumulated in lipid droplets (cellular organelles responsible for the storage and metabolism of neutral lipids and sterol esters). Our results demonstrate that changes in the structure of the imide substituent could affect the intracellular localization and the rate of release of chlorin p6 cycloimide derivatives from cells while preserving their high photodynamic activity. 相似文献
153.
The dynamics of serine/threonine protein kinase activity during the growth of the wild-type Streptomyces avermitilis strain and its chloramphenicol-resistant (Cmlr) pleiotropic mutant with an enhanced production of avermectins was studied by measuring the transfer of radiolabeled phosphate from [gamma-32P]ATP to the serine and threonine residues of proteins in cell-free extracts. In both of the strains studied, radiolabeled phosphate was found to incorporate into polypeptides with molecular masses of 32, 35, 41, 68, 75, 79, 83, and 137 kDa; however, the degree and the dynamics of phosphorylation of particular peptides were different in these strains. The differences revealed could not be accounted for by the interference of ATPases or phosphoprotein phosphatases. The data obtained may be interpreted as evidence that Cmlr mutation activates the protein kinase signalling system of S. avermitilis cells in the early stationary growth phase and thus enhances the production of avermectins and leads to some other physiological changes in the mutant strain. 相似文献
154.
155.
A short-term emotional-painful stress, experienced by pregnant rat females differing in threshold of excitability of their nervous system, was used to assess the state of interphase condensed chromatin and C-heterochromatin of neuron nuclei in developing brains of 16-17 day old embryos. To reveal relationships between the genetically determined excitability of rats and the state of interphase chromatin in their neuron nuclei a computer information system has been used that enabled us to classify the neuronal nuclei according to their specific DNA image cytometry features. The results indicate an obvious relationship between excitability of the nervous system and structural-functional state of the neuronal interphase chromatin. 相似文献
156.
157.
Formation probabilities of different hydrogen bonds between carbonyl oxygen and amide hydrogen were determined by Monte Carlo simulations using a computer model in the space of sterically allowable conformations of alanine and glycine oligopeptides, and the corresponding entropy losses for the peptide backbone, TS, were calculated. The model was studied at different criteria of steric interactions. Comparison with the data of other authors showed the values of TSto be mainly determined by overall extent and type of the state space and to be only slightly dependent on its energy profile. Both short-range and long-range steric interactions were shown to prevent hydrogen bonding, especially in alanine peptides. In the model studied, the initiation of (R)-helices is associated with TS= 8–10 kT, and prior formation of a 3/10-turn or one three-center H-bond does not appreciably decrease this entropy barrier. Elongation of the (R)-helix by one residue leads to TS= 3.0–3.7 kT, the helices begin to stabilize after at least three sequential H-bonds are formed. The difference in the probability of insertion of Ala and Gly into the helix is lower than it follows from comparison of their mobility. The results could be explained assuming that factors different from helical H-bonds take part in the stabilization of the helices. One may suppose upon modeling of folding that even three sequential H-bonds are unable to fix the structure of a flexible peptide loop, while the elongation of (R)-helices in the supersecondary helix-loop-helix structure is favorable as long as the loop conformation remains nearly optimal. 相似文献
158.
Lipopolysaccharide (LPS) is important for the virulence of Neisseria meningitidis, and is the target of immune responses. We took advantage of a monoclonal antibody (Mab B5) that recognises phosphoethanolamine (PEtn) attached to the inner core of meningococcal LPS to identify genes required for the addition of PEtn to LPS. Insertional mutants that lost Mab B5 reactivity were isolated and characterised, but failed to yield genes directly responsible for PEtn substitution. Subsequent genetic linkage analysis was used to define a region of DNA containing a single intact open reading frame which is sufficient to confer B5 reactivity to a B5 negative meningococcal isolate. The results provide an initial characterisation of the genetic basis of a key, immunodominant epitope of meningococcal LPS. 相似文献
159.
A new species of Leucocytozoon with gametocytes in fusiform host cells is described from the Bukharan great tit Parus bokharensis. It represents the first leucocytozoid in which the host cell nucleus is split into 2 more or less symmetrical portions, each located at an end of the host cell within its elongated fusiform processes. This species appears to be restricted with respect to geography and host. 相似文献
160.