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211.
The inhibitory effect of 23N-alkyl-4-piperidylesters (alkyl = ethyl-butyl) (APEA) and 8N-ethyl-2-pyrrolidinylmethylesters (EPMEA) of 2- and 3-substituted alkoxyphenylcarbamic acids (alkoxy = butoxy-heptyloxy-) on photosynthetic Hill reaction activity of spinach chloroplasts and on chlorophyll (Chl) synthesis in green algaeChlorella vulgaris was investigated. Inhibitory activities of these compounds were strongly connected with the lipophilicity of the whole molecule. A lower inhibitory activity of 2-alkoxy-substituted derivatives in relation to the corresponding 3-substituted ones was confirmed. Electron spin resonance (ESR) spectra of spinach chloroplasts demonstrated that the studied compounds affected the structure of photosystem (PS) 2 with the release of Mn2+ ions into interior of thylakoid membranes. 相似文献
212.
213.
Gómez-Coca Raquel B. Kapinos Larisa E. Holý Antonín Vilaplana Rosario A. González-Vílchez Francisco Sigel Helmut 《Journal of biological inorganic chemistry》2004,9(8):961-972
The acidity constants of the two-fold protonated acyclic 9-[2-(phosphonomethoxy)ethyl]-8-azaadenine, H2(9,8aPMEA)(+)(-), and its 8-isomer, 8-[2-(phosphonomethoxy)ethyl]-8-azaadenine, H2(8,8aPMEA)(+)(-), both abbreviated as H2(PA)(+)(-), as well as the stability constants of their M(H;PA)+ and M(PA) complexes with the metal ions M2+=Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ or Cd2+, have been determined by potentiometric pH titrations in aqueous solution at I=0.1 M (NaNO3) and 25 degrees C. Application of previously determined straight-line plots of log K(M)M(R-PO3) versus pK(H)H(R-PO3)for simple phosph(on)ate ligands, R-PO3(2-), where R represents a residue without an affinity for metal ions, proves that for all M(PA) complexes a larger stability is observed than is expected for a sole phosphonate coordination of the metal ion. This increased stability is attributed to the formation of five-membered chelates involving the ether oxygen present in the aliphatic residue (-CH2-O-CH2-PO3(2-)) of the ligands. The formation degrees of these chelates were calculated; they vary between about 13% for Ca(8,8aPMEA) and 71% for Cu(8,8aPMEA). The adenine residue has no influence on complex stability except in the Cu(9,8aPMEA) and Zn(9,8aPMEA) systems, where an additional stability increase attributable to the adenine residue is observed and equilibria between four different isomers exist. This means (1) an open isomer with a sole phosphonate coordination, M(PA)op, where PA(2-)=9,8aPMEA2-, (2) an isomer with a five-membered chelate involving the ether oxygen, M(PA)cl/O, (3) an isomer which contains five- and seven-membered chelates formed by coordination of the phosphonate group, the ether oxygen and the N3 site of the adenine residue, M(PA)cl/O/N3, and finally (4) a macrochelated isomer involving N7, M(PA)cl/N7. For Cu(9,8aPMEA) the formation degrees are 15, 30, 48 and 7% for Cu(PA)op, Cu(PA)cl/O, Cu(PA)cl/O/N3 and Cu(PA)cl/N7, respectively; this proves that the macrochelate involving N7 is a minority species. The situation for the Cu(PMEA) system, where PMEA2- represents the parent compound, i.e. the dianion of 9-[2-(phosphonomethoxy)ethyl]adenine, is quite similar. The relationship between the antiviral activity of acyclic nucleoside phosphonates and the structures of the various complexes is discussed and an explanation is offered why 9,8aPMEA is biologically active but 8,8aPMEA is not. 相似文献
214.
The stability constants of the 1 : 1 complexes formed between Pb2+ and several simple phosphate monoesters (4-nitrophenyl phosphate, phenyl phosphate, d-ribose 5-monophosphate, n-butyl phosphate) or phosphonate ligands (methylphosphonate, ethylphosphonate) (R-PO2–
3) were determined by potentiometric pH titrations in aqueous solution (25 °C;I=0.1 M, NaNO3). The construction of a log K
P
P
b
b(R-PO3) versus pK
H
H(R-PO3) plot for the mentioned ligand systems results in a straight line on which the data pairs (the corresponding equilibrium constants
were also measured) for uridine 5′-monophosphate (UMP2–) and thymidine 5′-monophosphate (dTMP2–) also fall; this result shows that in the Pb2+ complexes of UMP2– and dTMP2– the nucleobase residues do not interfere, in neither a positive nor a negative way, with the binding of Pb2+ and that the stability of all these complexes is determined by the basicity of the phosph(on)ate group. The mentioned straight-line
correlation (as defined by the least-squares procedure) allowed us to demonstrate (via constants determined now) that the
stability of the Pb2+ complex of cytidine 5′-monophosphate (CMP2–) is also solely determined by the basicity of its phosphate group. A similar evaluation, based on literature data, for the
Pb(HPO4) complex reveals that its stability corresponds closely to the expectations based on the Pb(R-PO3) data, though there is a slight hint that Pb(HPO4) may be somewhat more stable [which would be in agreement with previous observations of other M(HPO4) complexes]; clearly, more such comparisons are possible with the reference line given now. Based on the stability constants
of the monoprotonated Pb(H;CMP)+ complex and the Pb(cytidine)2+ species (which was also measured now), it is concluded that in Pb(H;CMP)+ the proton is located at the phosphate group and Pb2+ mainly at the N3/(C2)O site of the cytosine residue. Regarding nucleic acids in solution, it is further concluded that the
affinity of Pb2+ towards the negatively mono-charged phosphate unit, —O—P(O)2
–—O—, of a nucleic acid backbone is comparable to that of the cytosine moiety, the affinity towards other nucleobase residues
being smaller. This information may prove helpful regarding the properties of lead ribozymes.
Received: 16 April 1999 / Accepted: 2 June 1999 相似文献
215.
Berezhnoy D Baur R Gonthier A Foucaud B Goeldner M Sigel E 《Journal of neurochemistry》2005,92(4):859-866
Benzodiazepines are widely used for their anxiolytic, sedative, myorelaxant and anticonvulsant properties. They allosterically modulate GABA(A) receptor function by increasing the apparent affinity of the agonist GABA. We studied conformational changes induced by channel agonists at the benzodiazepine binding site. We used the rate of covalent reaction between a benzodiazepine carrying a cysteine reactive moiety with mutated receptor having a cysteine residue in the benzodiazepine binding pocket, alpha1H101Cbeta2gamma2, as a sensor of its conformation. This reaction rate is sensitive to local conformational changes. Covalent reaction locks the receptor in the conformation stabilized by positive allosteric modulators. By using concatenated subunits we demonstrated that the covalent reaction occurs either exclusively at the alpha/gamma subunit interface, or if it occurs in both alpha1 subunits, exclusively reaction at the alpha/gamma subunit interface can modulate the receptor. We found evidence for an increased rate of reaction of activated receptors, whereas reaction rate with the desensitized state is slowed down. The benzodiazepine antagonist Ro15-1788 efficiently inhibited the covalent reaction in the presence of 100 microm GABA but only partially in its absence or in the presence of 10 microm GABA. It is concluded that Ro15-1788 efficiently protects activated and desensitized states, but not the resting state. 相似文献
216.
Schaerer MT Kannenberg K Hunziker P Baumann SW Sigel E 《The Journal of biological chemistry》2001,276(28):26597-26604
gamma-Aminobutyric acid type A (GABA(A)) receptors were immunopurified from bovine brain using a monoclonal antibody directed against the alpha1 subunit. Of the several proteins that copurified, a 34-kDa protein was analyzed further. After enrichment and tryptic proteolysis, the resulting fragments were sequenced, and the protein was identified as gC1q-R. Using anti-gC1q-R and anti-GABA(A) receptor antibodies, mutual coimmunoprecipitation could be demonstrated from solubilized rat brain membranes. The stability of this interaction was estimated to be very high. Using the yeast two-hybrid system, various GABA(A) receptor subunit intracellular loop constructs were tested for an interaction with gC1q-R. All beta subunits, but not alpha 1 and gamma 2 subunits, were found to bind to gC1q-R. NH(2)- and COOH-terminally truncated beta 2 subunit loops were used to find the region responsible for the interaction with gC1q-R. A stretch of 15 amino acids containing 7 positively charged residues was identified (amino acids 399--413). This region contains residue Ser-410, which is a protein kinase substrate, and it is known that phosphorylation of this residue leads to an alteration in receptor activity. Localization studies suggested a predominantly intracellular localization. Our observations therefore suggest a tight interaction between gC1q-R and the GABA(A) receptor which might be involved in receptor biosynthesis or modulation of the mature function. 相似文献
217.
The mutagenicity of metal species may be the result of a direct interaction with the target molecule DNA. Possible scenarios leading to nucleobase mispairing are discussed, and selected examples are presented. They include changes in nucleobase selectivity as a consequence of alterations in acid-base properties of nucleobase atoms and groups involved in complementary H bond formation, guanine deprotonation, and stabilization of rare nucleobase tautomers by metal ions. Oxidative nucleobase damage brought about by metal species will not be considered. 相似文献
218.
The method of affinity coelectrophoresis was used to study the binding of
nine representative glycosaminoglycan (GAG)-binding proteins, all thought
to play roles in nervous system development, to GAGs and proteoglycans
isolated from developing rat brain. Binding to heparin and non-neural
heparan and chondroitin sulfates was also measured. All nine
proteins-laminin-1, fibronectin, thrombospondin-1, NCAM, L1, protease
nexin-1, urokinase plasminogen activator, thrombin, and fibroblast growth
factor-2-bound brain heparan sulfate less strongly than heparin, but the
degree of difference in affinity varied considerably. Protease nexin-1
bound brain heparan sulfate only 1.8- fold less tightly than heparin
(Kdvalues of 35 vs. 20 nM, respectively), whereas NCAM and L1 bound heparin
well (Kd approximately 140 nM) but failed to bind detectably to brain
heparan sulfate (Kd>3 microM). Four proteins bound brain chondroitin
sulfate, with affinities equal to or a few fold stronger than the same
proteins displayed toward cartilage chondroitin sulfate. Overall, the
highest affinities were observed with intact heparan sulfate proteoglycans:
laminin-1's affinities for the proteoglycans cerebroglycan (glypican-2),
glypican-1 and syndecan-3 were 300- to 1800-fold stronger than its affinity
for brain heparan sulfate. In contrast, the affinities of fibroblast growth
factor-2 for cerebroglycan and for brain heparan sulfate were similar.
Interestingly, partial proteolysis of cerebroglycan resulted in a >400-
fold loss of laminin affinity. These data support the views that (1)
GAG-binding proteins can be differentially sensitive to variations in GAG
structure, and (2) core proteins can have dramatic, ligand-specific
influences on protein-proteoglycan interactions.
相似文献
219.
Contrasting population structure from nuclear intron sequences and mtDNA of humpback whales 总被引:21,自引:4,他引:21
Powerful analyses of population structure require information from multiple
genetic loci. To help develop a molecular toolbox for obtaining this
information, we have designed universal oligonucleotide primers that span
conserved intron-exon junctions in a wide variety of animal phyla. We test
the utility of exon-primed, intron-crossing amplifications by analyzing the
variability of actin intron sequences from humpback, blue, and bowhead
whales and comparing the results with mitochondrial DNA (mtDNA) haplotype
data. Humpback actin introns fall into two major clades that exist in
different frequencies in different oceanic populations. It is surprising
that Hawaii and California populations, which are very distinct in mtDNAs,
are similar in actin intron alleles. This discrepancy between mtDNA and
nuclear DNA results may be due either to differences in genetic drift in
mitochondrial and nuclear genes or to preferential movement of males, which
do not transmit mtDNA to offspring, between separate breeding grounds.
Opposing mtDNA and nuclear DNA results can help clarify otherwise hidden
patterns of structure in natural populations.
相似文献
220.
Thais Russo-Abrahão Carolina Macedo Koeller Michael E. Steinmann Stephanie Silva-Rito Thaissa Marins-Lucena Michele Alves-Bezerra Naira Ligia Lima-Giarola Iron Francisco de-Paula Amaia Gonzalez-Salgado Erwin Sigel Peter Bütikofer Katia Calp Gondim Norton Heise José Roberto Meyer-Fernandes 《Journal of bioenergetics and biomembranes》2017,49(2):183-194