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1.
Natalia V. Sumbatyan Karsten Gröger Oleg N. Chichenkov Galina A. Korshunova 《International journal of peptide research and therapeutics》1997,4(4-6):477-480
Summary Solid phase syntheses of analogues of the opioid heptapeptide dermorphin (H-Tyr-dAla-Phe-Gly-Tyr-Pro-Ser-NH2) containing in the first position 3-aminotyrosine, 3-nitrotyrosine, 4-aminophenylalanine, or nucleoamino acids, 3-(uracilyl-1)alanine,
3-(thyminyl-1)alanine and 3-(6-methyluracilyl-1)alanine are described. The receptor binding properties and analgesic activity
of the analogues were examined in comparison with dermorphin. All analogues showed low opioid activity in the binding assays
with respect to μ- and δ-receptors. The peptide containing 3-(thyminyl-1)alanine demonstrated a high analgesic activity in
different tests when administered intracisternally in mice. 相似文献
2.
Summary L-Alanine binds to and activates specific taste receptors ofIctalurus punctatus, the channel catfish. In order to determine the structural requirements for receptor binding and activation in this model system, a number of analogues of L-alanine were tested using a neurophysiological assay and a competitive ligand binding assay. These assays measured the ability of analogues to activate taste receptors and to displace L-[3H]alanine from L-alanine binding sites. Of those derivatives with modifications of the sidechain, L-serine, glycine,-chloro-L-alanine and 1-amino-cyclopropane-1-carboxylic acid were the most potent analogues with IC50s similar to and neural responses slightly decremented from that of L-alanine. Derivatives containing branched sidechains or sidechains of otherwise increased volume were considerably less active. All modifications of the-carboxylic acid and the-amine, including amides, esters and various isosteres, led to substantial reduction in the analogues' ability to displace L-[3H]alanine and, in most cases, very weak stimulatory capability. However, L-lactic acid was a reasonably strong stimulus, but a poor competitor, suggesting that it acts at a different receptor site. Overall, these results indicate the importance of the charged amine and carboxylic acid groups for binding to and activation of the receptor for L-alanine. Moreover, modifications around the chiral center of L-alanine support the hypothesis that receptor binding and activation are separate processes in this model taste system. 相似文献
3.
《Bioorganic & medicinal chemistry》2014,22(7):2333-2338
Analogues of [Dmt1]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt = 2′,6′-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity, were prepared by replacing Phe3 with various 2′,6′-dialkylated Phe analogues, including 2′,6′-dimethylphenylalanine (Dmp), 2′,4′,6′-trimethylphenylalanine (Tmp), 2′-isopropyl-6′-methylphenylalanine (Imp) and 2′-ethyl-6′-methylphenylalanine (Emp), or with the bulky amino acids 3′-(1-naphthyl)alanine (1-Nal), 3′-(2-naphthyl)alanine (2-Nal) or Trp. Several compounds showed significantly increased μ agonist potency, retained μ receptor selectivity and are of interest as drug candidates for neuropathic pain treatment. Surprisingly, the Dmp3-, Imp3-, Emp3- and 1-Nal3-containing analogues showed much increased κ receptor binding affinity and had mixed μ/κ properties. In these cases, molecular dynamics studies indicated conformational preorganization of the unbound peptide ligands due to rotational restriction around the CβCγ bond of the Xxx3 residue, in correlation with the observed κ receptor binding enhancement. Compounds with a mixed μ/κ opioid activity profile are known to have therapeutic potential for treatment of cocaine abuse. 相似文献
4.
A novel lectin from the mushroom Marasmius oreades (MOA) has been shown to bind to human blood group B oligosaccharides [1]. In the present work we examine the binding of a series of analogues of the blood group B-trisaccharide, Gal(1-3)[Fuc(1-2)]Gal-OR (1, R = (CH2)8COOMe). MOA was biotinylated and immobilized on a micro column (9.8 L) for evaluation by Frontal Affinity Chromatography-Mass Spectrometry (FAC-MS) [2]. The trisaccharide 1 was found to be the epitope needed for maximum recognition (K
d = 3.6 M). A series of synthetic deoxygenated and O-methylated analogues of the B-trisaccharide (R = OMe) were then screened against the lectin, and the key structural elements for binding were determined. OH-4 of the -Gal residue and OH-2 of the -Gal residue were found to be critical for recognition. The FAC-MS technique also proved powerful in evaluating mixtures of compounds. Since the solution NMR structure and crystal structure of the B-trisaccharide are known [3], we propose the specific surface of the trisaccharide that is recognized by the lectin. Published in 2003. 相似文献
5.
Shanshan Wang Yufeng Sun Shaoqing Du Yaoguo Qin Hongxia Duan Xinling Yang 《Journal of molecular modeling》2016,22(6):144
Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-β-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized π–π and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1–D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure. 相似文献
6.
Summary The structure-activity data of 6 years on 395 analogs of the luteinizing hormone releasing hormone (LHRH) have been studied to determine effective substituents for the ten positions for maximal antiovulatory activity and minimal histamine release. The numbers of substituents studied in the ten positions are as follows: (41)1-(12)2-(12)3-(5)4-(47)5-(52)6-(16)7-(18)8-(4)9-(8)10. In position 1, DNal and DQal were effective with the former being more frequently the better substituent. DpClPhe was uniquely effective in position 2. Positions 3 and 4 are very sensitive to change. D3Pal in position 3 and Ser in position 4 of LHRH were in the best antagonists. PicLys and cPzACAla were the most successful residues in position 5 with cPzACAla being the better substituent. Position 6 was the most flexible and many substituents were effective; particularly DPicLys. Leu7 was most often present in the best antagonists. In position 8, Arg was effective for both antiovulatory activity and histamine release; ILys was effective for potency and lesser histamine release. Pro9 of LHRH was retained. DAlaNH2
10 was in the best antagonists.Abbreviations AABLys
N
-(4-acetylaminobenzoyl)lysine
- AALys
N
-anisinoyl-lysine
- AAPhe
3-(4-acetylaminophenyl)lysine
- Abu
2-aminobutyric acid
- ACLys
N
-(6-aminocaproyl)lysine
- ACyh
1-aminocyclohexanecarboxylic acid
- ACyp
1-aminocyclopentanecarboxylic acid
- Aile
alloisoleucine
- AnGlu
4-(4-methoxy-phenylcarbamoyl)-2-aminobutyric acid
- 2ANic
2-aminonicotinic acid
- 6ANic
6-aminonicotinic acid
- APic
6-aminopicolinic acid
- APh
4-aminobenzoic acid
- APhe
4-aminophynylalanine
- APz
3-amino-2-pyrazinecarboxylic acid
- Aze
azetidine-2-carboxylic acid
- Bim
5-benzimidazolecarboxylic acid
- BzLys
N
-benzoyllysine
- Cit
citrulline
- Cl2Phe
3-(3,4-dichlorphenyl)alanine
- cPzACAla
cis-3-(4-pyrazinylcarbonylaminocyclohexyl)alnine
- cPmACAla
cis-3-[4-(4-pyrimidylcarbonyl)aminocyclohexyl]alanine
- Dbf
3-(2-dibenzofuranyl)alanine
- DMGLys
N
-(N,N-dimethylglycyl)lysine
- Dpo
N
-(4,6-dimethyl-2-pyrimidyl)-ornithine
- F2Ala
3,3-difluoroalanine
- hNal
4-(2-naphthyl)-2-aminobutyric acid
- HOBLys
N
-(4-hydroxybenzoyl)lysine
- hpClPhe
4-(4-chlorophenyl)-2-amino-butyric acid
- Hse
homoserine, 2-amino-4-hydroxybutanoic acid
- ICapLys
N
-(6-isopropylaminocaproyl)lysine
- ILys
N
-isopropyllysine
- Ind
indoline-2-carboxylic acid
- INicLys
N
-isonicotinoyllysine
- IOrn
N
-isopropylornithine
- Me3Arg
NG,NG,NG-trimethylarginine
- Me2Lys
N
,N
-dimethyllysine
- MNal
3-[(6-methyl)-2-naphtyl]alanine
- MNicLys
N
-(6-methylpicolinoyl)lysine
- MPicLys
N
-(6-methylpicolinoyl)lysine
- MOB
4-methoxybenzoyl
- MpClPhe
N-methyl-3-(4-chlorphenyl)lysine
- MPZGlu
glutamic acid,-4-methylpiperazine
- Nal
3-(2-naphthyl)alanine
- Nap
2-naphthoic acid
- NicLys
N
-nicotinoyllysine
- NO2B
4-nitrobenzoyl
- NO2Phe
3-(4-nitrophenyl)alanine
- oClPhe
3-(2-chlorphenyl)alanine
- Opt
O-phenyl-tyrosine
- Pal
3-(3-pyridyl)alanine
- 2Pal
3-(2-pyridyl)alanine
- 2PALys
N
-(3-pyridylacetyl)lysine
- pCapLys
N
-(6-picolinoylaminocaproyl)lysine
- pClPhe
3-(4-chlorophenyl)alanine
- pFPhe
3-(4-fluorophenyl)-alanine
- Pic
picolinic acid
- PicLys
N
-picolinoyllysine
- Pip
piperidine-2-car-boxylic acid
- PmcLys
N
-(4-pyrimidylcarbonyl)lysine
- Ptf
3-(4-trifluromethyl phenyl)alanine
- Pz
pyrazinecarboxylic acid
- PzAla
3-pyrazinylalanine
- PzAPhe
3-(4-pyrazinylcarbonylaminophenyl)alanine
- Qal
3-(3-quinolyl)alanine
- Qnd-Lys
N
-quinaldoyllysine
- Qui
3-quinolinecarboxylic acid
- Qux
2-quinoxalinecarboxylic acid
- Tic
1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
- TinGly
2-thienylglycine
- tNACAla
trans-3-(4-nicotinoylaminocyclohexyl)-alanine
- tPACAla
trans-3-(4-picolinoylaminocyclohexyl)alanine 相似文献
7.
Summary Several LHRH antagonists with trans-3-(4-pyrazinylcarbonylaminocyclohexyl)alanine (trans-PzACAla) in the position 5 were synthesized and their antiovulatory activity was compared with the activity of the analogs containing cis-PzACAla in this position. In all cases cis-isomer produced more potent analogs. Introduction of cis-PzACAla in the position 5 of Antide gave Antide B which completely inhibits ovulation at a dose of 0.5µg/rat. Antide B releases negligible histamine (ED50 = 104µg/mL), and has excellent solubility in water. Also, an improved synthesis of cis-PzACAla is reported, involving the hydrogenation of 4-aminophenylalanine on a rhodium catalyst to give the desired cis-isomer with a 53% yield.Abbreviations Cpa
3-(4-chlorophenyl)alanine
- ILys
N-isopropyllysine
- Nal
3-(2-naphthyl)alanine
- NicLys
N-nicotinoyllysine
- Pal
3-(3-pyridyl)alanine
- PicLys
N-picolinoyllysine
- PzACAla
3-(4-pyrazinylcarbonylaminocyclohexyl)alanine
- Qal
3-(3-quinolyl)alanine 相似文献
8.
Pham Dinh Quoc Huy Yao-Chung Yu Son Tung Ngo Tran Van Thao Chin-piao Chen Mai Suan Li Yi-Cheng Chen 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Aggregation of amyloid-beta (Aβ) has been proposed as the main cause of Alzheimer's disease (AD). Vitamin K deficiency has been linked to the pathogenesis of AD. Therefore, 15 synthesized vitamin K3 (VK3) analogues were studied for their anti-amyloidogenic activity.Methods
Biological and spectroscopic assays were used to characterize the effect of VK3 analogues on amyloidogenic properties of Aβ, such as aggregation, free radical formation, and cell viability. Molecular dynamics simulation was used to calculate the binding affinity and mode of VK3 analogue binding to Aβ.Results
Both numerical and experimental results showed that several VK3 analogues, including VK3-6, VK3-8, VK3-9, VK3-10, and VK3-224 could effectively inhibit Aβ aggregation and conformational conversion. The calculated inhibition constants were in the μM range for VK3-10, VK3-6, and VK3-9 which was similar to the IC50 of curcumin. Cell viability assays indicated that VK3-9 could effectively reduce free radicals and had a protective effect on cytotoxicity induced by Aβ.Conclusions
The results clearly demonstrated that VK3 analogues could effectively inhibit Aβ aggregation and protect cells against Aβ induced toxicity. Modified VK3 analogues can possibly be developed as effective anti-amyloidogenic drugs for the treatment of AD.General significance
VK3 analogues effectively inhibit Aβ aggregation and are highly potent as anti-amyloidogenic drugs for therapeutic treatment of AD. 相似文献9.
A known selective agonist of the A3 adenosine receptors (AR), MRS1898 [(1′R,2′R,3′S,4′R,5′S)-4-{2-chloro-6-[(3-iodophenylmethyl)amino]purin-9-yl}-1-(methylaminocarbonyl)bicyclo[3.1.0]hexane-2,3-diol], was synthesized in radioactive form and characterized pharmacologically. This agonist ligand series, based on nucleoside analogues containing a rigid, bicyclic ring system in place of the ribose moiety, was selected for radiolabeling due to its high A3AR affinity across species, with nanomolar binding at both rat and human A3ARs. The radioiodination of MRS1898 on its N6–3-iodobenzyl substituent was accomplished in 76% radiochemical yield by iododestannylation of a 3-(trimethylstannyl)benzyl precursor. [125I]MRS1898 bound to the rat A3AR with a Kd value of 0.17±0.04 nM and a Bmax value of 0.66±0.15 pmol/mg protein. The competition binding profiles for other agonists and antagonists obtained with this radioligand are similar to those previously obtained with other radioligands. The advantages of [125I]MRS1898 compared with previously used radioligands are primarily its high selectivity and affinity for the rat A3AR and also its facile synthesis and radiochemical stability; however, a relatively high level of nonspecific binding presents a limitation. Thus, we have introduced the first selective radioligand for the rat A3AR. 相似文献
10.
A. M. López-Colomé 《Neurochemical research》1981,6(9):1019-1033
Binding ofl-[3H]glutamate to membranes from whole chick retina and from subcellular fractions enriched with photoreceptor terminals (P1), or terminals from the inner plexiform layer (P2) was studied. Na+-dependent and Na+-independent binding to these membranes was demonstrated. Na+-independent binding was stereospecific. Kinetic analysis of the binding process indicated a single high-affinity system (K
B=0.55 M) with a capacity of approximately 20 pmoles/mg protein in all the membrane fractions. [3H]Glutamate binding to P1 and P2 fractions was effectively displaced by several structural analogues of glutamate. Glutamate diethyl-ester appreciably displaced binding, whereas kainic acid did not displace bound glutamate. Data indicate the binding of [3H]glutamate to physiologically relevant receptors in the chick retina. 相似文献
11.
Summary The amino acid, D-2-naphthylalanine, has been used by many investigators as a substituent for position one of antagonists of LHRH. We have newly designed substituents for position one in which the carboxy groups of 2-naphthoic acid, 3-quinoline- and 2-quinoxaline-carboxylic acids are linked to the five amino acids, DAla, DThr, DNVal, DSer, and Gly. The substituents in positions 2–10 were DpClPhe2, DPal3, Ser4, PicLys5, DPicLys6, Leu7, ILys8, Pro9, DAlaNH2
10.Remarkably, DThr, acylated on the amino group by 3-quinolinecarboxylic acid or by 3-quinoxalinecarboxylic acid, and introduced into position one of a relatively potent antagonist, gave a new class of antagonists of LHRH, which released as little histamine as yet recorded, and yet possessed reasonable antiovulatory activity and greatly improved solubility.These structure-activity results advance the basic knowledge of understanding the structural features of such decapeptides which cause antiovulatory activity and histamine release.Abbreviations ILys
N
-isopropyllysine;
- 1-Nal
3-(1-naphthyl)alanine
- 2-Nal
3-(2-naphthyl)alanine
- Nap
2-naphthoic acids
- NicLys
N
-nicotinoyllysine;
- Pal
3-(3-pyridyl)alanine
- pClPhe
3-(4-chlorophenyl)alanine
- PicLys
N
-picolinoyllysine
- c-PzACAla
cis-3-(4-pyrazinylcarbonylaminocyclohexyl) alanine
- 3-Qal
3-(3-quinolyl)alanine
- Qui
3-quinolinecarboxylic acid
- Qux
2-quinoxalinecarboxylic acid 相似文献
12.
13.
Interference of S-Alkyl Derivatives of Glutathione with Brain Ionotropic Glutamate Receptors 总被引:1,自引:0,他引:1
Zsolt Jenei Réka Janáky Vince Varga Pirjo Saransaari Simo S. Oja 《Neurochemical research》1998,23(8):1085-1091
The effects of glutathione, glutathione sulfonate and S-alkyl derivatives of glutathione on the binding of glutamate and selective ligands of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA receptors were studied with mouse synaptic membranes. The effects of glutathione and its analogues on 45Ca2+ influx were also estimated in cultured rat cerebellar granule cells. Reduced and oxidized glutathione, glutathione sulfonate, S-methyl-, -ethyl-, -propyl-, -butyl- and -pentylglutathione inhibited the Na+-independent binding of L-[3H]glutamate. They strongly inhibited also the binding of (S)-2-amino-3-hydroxy-5-[3H]methyl-4-isoxazolepropionate [3H]AMPA (IC50 values: 0.8–15.9 M). S-Alkylation of glutathione rendered the derivatives unable to inhibit [3H]kainate binding. The NMDA-sensitive binding of L-[3H]glutamate and the binding of 3-[(R)-2-carboxypiperazin-4-yl][1,2-3H]propyl-1-phosphonate ([3H]CPP, a competitive antagonist at NMDA sites) were inhibited by the peptides at micromolar concentrations. The strychnine-insensitive binding of the NMDA coagonist [3H]glycine was attenuated only by oxidized glutathione and glutathione sulfonate. All peptides slightly enhanced the use-dependent binding of [3H]dizocilpine (MK-801) to the NMDA-gated ionophores. This effect was additive with the effect of glycine but not with that of saturating concentrations of glutamate or glutamate plus glycine. The glutamate- and NMDA-evoked influx of 45Ca2+ into cerebellar granule cells was inhibited by the S-alkyl derivatives of glutathione. We conclude that besides glutathione the endogenous S-methylglutathione and glutathione sulfonate and the synthetic S-alkyl derivatives of glutathione act as ligands of the AMPA and NMDA receptors. In the NMDA receptor-ionophore these glutathione analogues bind preferably to the glutamate recognition site via their -glutamyl moieties. 相似文献
14.
The activities of several enzymes, including ribulose-1,5-diphosphate (RuDP) carboxylase (EC 4.1.1.39) and phosphoenolpyruvate (PEP) carboxylase (EC 4.1.1.31) were measured as a function of leaf age in Z. mays. Mature leaf tissue had a RuDP-carboxylase activity of 296.7 mol CO2 g-1 fresh weight h-1 and a PEP-carboxylase activity of 660.6 mol CO2 g-1 fresh weight h-1. In young corn leaves the activity of the two enzymes was 11 and 29%, respectively, of the mature leaves. In senescent leaf tissue, RuDP carboxylase activity declined more rapidly than that of any of the other enzymes assayed. On a relative basis the activities of NADP malic enzyme (EC 1.1.1.40), aspartate (EC 2.6.1.1) and alanine aminotransferase (EC 2.6.1.2), and NAD malate dehydrogenase (EC 1.1.1.37) exceeded those of both PEP and RuDP carboxylase in young and senescent leaf tissue. Pulse-chase labeling experiments with mature and senescent leaf tissue show that the predominant C4 acid differs between the two leaf ages. Labeling of alanine in senescent tissue never exceeded 4% of the total 14C remaining during the chase period, while in mature leaf tissue alanine accounted for 20% of the total after 60 s in 12CO2. The activity of RuDP carboxylase during leaf ontogeny in Z. mays parallels the development of the activity of this enzyme in C3 plants.Abbreviations RuDP
ribulose-1,5-diphosphate
- PEP
phosphoenol pyruvate
- PGA
3-phosphoglycerate 相似文献
15.
E. N. Zografou G. J. Tsiropoulos L. H. Margaritis 《Entomologia Experimentalis et Applicata》1998,87(2):125-132
The effect of twenty five amino acid analogues at various concentrations upon the adult olive fruit fly Bactrocera oleae Gmelin (Diptera: Tephritidae), was tested. Insect survival was significantly shortened by the following amino acid analogues: (in parentheses are indicated the antagonized amino acids) D-cycloserine (alanine), L-glutamic acid--hydrazide (glutamine), DL-allyl-glycine (cysteine), L-canavanine (arginine), L-methionine-DL-sulfoximine (methionine) and 3,4-dehydro-DL-proline (proline). Fecundity was significantly reduced by the same analogues plus aminoethanesulfonic acid (glycine), taurine (alanine), L-norvaline (leucine), a-methyl-DL-serine (serine), DL-hydroxyglutamic acid (glutamic acid), (S)-2-(aminoethyl)-L-cysteine (lysine), a-methyl-DL-methionine (methionine) and a-methyl-DL-histidine (histidine). All the above amino acid analogues also depressed egg-hatching with the exception of taurine, DL-hydroxyglutamic acid, DL-allyl glycine, a-methyl-DL-methionine and a-methyl-DL-histidine. Finally, y-glutamyl-p-nitroanilide (glutamic acid), crotyl-glycine (methionine), DL-7-azatryptophan and 5-methyl-DL-tryptophan (tryptophan), DL-1,2,4 triazole-3-alanine (histidine) and DL-pipecolic acid (proline) did not affect any of the parameters tested. 相似文献
16.
Fredholm BB Assender JW Irenius E Kodama N Saito N 《Cellular and molecular neurobiology》2003,23(3):379-400
1. The effect of adenosine analogues and of nucleotides, alone or in combination, on intracellular calcium, accumulation of inositol (1,4,5) trisphosphate (InsP3), and on activation of protein kinase C (PKC) was studied in DDT1 MF2 cells derived from a Syrian hamster myosarcoma. These cells were found to express mRNA for A1 and some as yet unidentified P2Y receptor(s).2. Activation of either receptor type stimulated the production of InsP3 and raised intracellular calcium in DDT1 MF2 cells. Similarly, the A1 selective agonist N6-cyclopentylade- nosine (CPA) increased PKC-dependent phosphorylation of the substrate MBP4–14 and induced a PKC translocation to the plasma membrane as determined using [3H]-phorbol dibutyrate (PDBu) binding in DDT1 MF-2 cells. However, neither adenosine nor CPA induced a significant translocation of transiently transfected -PKC-GFP from the cytosol to the cell membrane. In contrast to adenosine analogues, ATP and UTP also caused a rapid but transient translocation of -PKC-GFP and activation of PKC.3. Doses of the A1 agonist CPA and of ATP or UTP per se caused barely detectable increases in intracellular Ca2+ but when combined, they caused an almost maximal stimulation. Similarly, adenosine (0.6 M) and UTP (or ATP, 2.5 M), which per se caused no detectable translocation of either - or -PKC-GFP, caused when combined a very clear-cut translocation of both PKC subforms, albeit with different time courses. These results show that simultaneous activation of P2Y and adenosine A1 receptors synergistically increases Ca2+ transients and translocation of PKC in DDT1 MF-2 cells. Since adenosine is rapidly formed by breakdown of extracellular ATP, such interactions may be biologically important. 相似文献
17.
Cellular redox state and activating protein-1 are involved in ascorbate effect on calcitriol-induced differentiation 总被引:1,自引:0,他引:1
G. López-Lluch M. -V. Blázquez R. Pérez-Vicente A. Macho M. I. Burón F. J. Alcaín E. Muñoz P. Navas 《Protoplasma》2001,217(1-3):129-136
Summary Ascorbate has been related to the differentiation of several mesenchymal cells including haematopoietic cells. We have previously demonstrated that ascorbate enhances the activity of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on monocytic differentiation of HL-60 cells. Here, we show that ascorbate-mediated modification of cellular redox state and AP-1 (activating protein-1) DNA binding during early phases are related to the enhancing effect of ascorbate on differentiation. Ascorbate, but not its fully oxidized form, dehydroascorbate, or an ascorbate analogue with a low rate of oxidation, ascorbate-2-phosphate, enhanced the differentiation induced by 1,25(OH)2D3, modified cytosolic reactive oxygen species levels and mitochondrial redox potential (m), and modulated AP-1 DNA binding in HL-60 cells. Ascorbate itself increased AP-1 binding to DNA in noninduced cells, whereas it inhibited AP-1 binding in 1,25(OH)2D3-induced cells. However, ascorbate increased the mRNA levels ofc-jun, junB. andc-fos in 1,25(OH)2D3-induced cells. Taken together, these results suggest that the enhancing effect of ascorbate on HL-60 differentiation induced by 1,25(OH)2D3 is related to its effect on the cellular redox state and the modulation of AP-1 activity.Abbreviations 1,25-(OH)2D3
1,25-dihydroxyvitamin D3
- m
mitochondrial transmembrane potential
- AP-1
activating protein-1
- Asc-2-P
ascorbate-2-phosphate
- DHA
dehydroascorbate
- DiOC6(3)
3,3-dihexyloxacarboxyanine iodide
- EMSA
electromobility shift assay
- NBT
nitroblue tetrazolium
- ROS
reactive oxygen species 相似文献
18.
Influenza A and Sendai viruses bind toneolacto-series gangliosides isolated from human granulocytes. Differences in receptor specificity of influenza viruses A/PR/8/34 (H1N1), A/X-31 (H3N2), and parainfluenza Sendai virus (HNF1, Z-strain) were determined by two direct solid phase binding assays: the overlay technique, which combines high-resolution in the separation of gangliosides on thin-layer chromatograms with direct binding; and the microwell adsorption assay as a convenient binding assay which is performed in microtitre wells to estimate the avidity of binding to an isolated ganglioside. Both methods were applied for comparative binding studies. Viruses were found to exhibit specificity for oligosaccharides and sialic acids as well as for chain length of the neutral carbohydrate backbone, whereas differing fatty acids (C24:1 and C16:0) in the ceramide portion had no impact on virus adsorption. Terminal sialyloligosaccharides Neu5Ac2-3Gal1-4Glc-R of GM3, and Neu5Ac2-3Gal1-4GlcNAc-R as well as Neu5Ac2-6Gal1-4GlcNAc-R ofneolacto-series gangliosides with nLcOse4Cer and nLcOse6Cer backbone, exhibited significant specific receptor activity towards the different viruses. To compare the data revealed from both test systems, values of virus binding were ascertained by a non-parametric statistical approach based on rank correlation. The rank correlation coefficientr
s was calculated according to Spearman from each virus binding towards GM3, IV3Neu5Ac-nLcOse4Cer, IV6Neu5Ac-nLcOse4Cer and VI3Neu5Ac-nLcOse6SCer. The rank correlation coefficients 0.74, 0.95 and 0.92, which were determined for A/PR/8/34 (H1N1), A/X-31 (H3N2) and Sendai virus (HNF1, Z-strain), respectively, indicated that both assays generate highly correlated experimental data. Based on these results, analyses of virus binding on thin-layer chromatograms as well as in microwells were found equivalent tools for ganglioside receptor studies.
Abbreviations: BSA, bovine serum albumin; GSL(s), glycosphingolipids; HPTLC, high performance thin-layer chromatography; PBS, phosphate buffered saline; Neu5Ac,N-acetylneuraminic acid [35];r
s = rank correlation coefficient according to Spearman. The designation of the glycosphingolipids follows the IUPAC-IUB recommendations [36]. LacCer or lactosylceramide, Gal1-4Glc1-1Cer; lacto-N-neotetraosylceramide or nLcOse4Cer, Gal1-4GlcNAc1-3Gal1-4Glc1-1Cer; lacto-N-norhexaosylceramide or nLcOse6Cer, Gal1-4GlcNAc1-3Gal1-4GlcNAc1-3Gal1-4Glc1-1Cer; GM3 (according to Svennerholm [37]) or II3Neu5AcLacCer. 相似文献
19.
Katsuhiro Kawashiro Shigeaki Seno Shigeru Sugiyama Hiromu Hayashi 《Origins of life and evolution of the biosphere》1993,23(3):153-165
The reactions of 2- and 3-aminopropionitrile (APN), and 2,2-iminodipropionitrile (IDPN) were carried out in aqueous ammoniacal media. 2-APN was found to give IDPN, N-(1-cyanoethyl)alanine amide, N-(1-cyanoethyl)alanine, N-(1-carbamoylethyl)alanine, 2,2-iminodipropionic acid, alanine amide, and alanine. Compounds of biological significance such as peptides and amino acids other than alanine were not formed. The results were well consistent with those obtained for aminoacetonitrile. IDPN which can be formed easily from 2-APN in aqueous media, also yielded the same products as with 2-APN. On the other hand, 3-APN gave 3-alanine via 3-alanine amide under similar conditions. 3-APN was found to be more stable than 2-APN in aqueous media. 相似文献
20.
Sumeet R. Singh Fida Ahmad Avtar Lal Changhua Yu Zemin Bai Heather Bennett 《CMAJ》2009,180(4):385-397