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1.
《Bioorganic & medicinal chemistry letters》2014,24(18):4466-4471
A novel synthesis of the translocator protein (TSPO) ligand 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (SSR180575, 3) was achieved in four steps from commercially available starting materials. Focused structure–activity relationship development about the pyridazinoindole ring at the N3 position led to the discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (14), a novel ligand of comparable affinity. Radiolabeling with fluorine-18 (18F) yielded 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[18F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide ([18F]-14) in high radiochemical yield and specific activity. In vivo studies of [18F]-14 revealed this agent as a promising probe for molecular imaging of glioma. 相似文献
2.
Naresh Sunduru Mona Svensson Mariateresa Cipriano Sania Marwaha C. David Andersson Richard Svensson 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):513-521
Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4g, with an IC50 of 2.6?µM as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4i, with an IC50 of 0.35?µM. 相似文献
3.
Lukas K. Filak Gerhard Mühlgassner Michael A. Jakupec Petra Heffeter Walter Berger Vladimir B. Arion Bernhard K. Keppler 《Journal of biological inorganic chemistry》2010,15(6):903-918
The synthesis of ruthenium(II) and osmium(II) arene complexes with the closely related indolo[3,2-c]quinolines N-(11H-indolo[3,2-c]quinolin-6-yl)-ethane-1,2-diamine (L
1
) and N′-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (L
2
) and indolo[3,2-d]benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-ethane-1,2-diamine (L
3
) and N′-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N,N-dimethylethane-1,2-diamine (L
4
) of the general formulas [(η6-p-cymene)MII(L
1
)Cl]Cl, where M is Ru (4) and Os (6), [(η6-p-cymene)MII(L
2
)Cl]Cl, where M is Ru (5) and Os (7), [(η6-p-cymene)MII(L
3
)Cl]Cl, where M is Ru (8) and Os (10), and [(η6-p-cymene)MII(L
4
)Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass
spectrometry, spectroscopy (IR, UV–vis, and NMR), and X-ray crystallography (L
1
·HCl, 4·H2O, 5, and 9·2.5H2O). Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells as well as cyclin-dependent
kinase (cdk) inhibition and DNA intercalation in cell-free settings have been established. The metal-free indolo[3,2-c]quinolines inhibit cancer cell growth in vitro, with IC50 values in the high nanomolar range, whereas those of the related indolo[3,2-d]benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of
cdk2/cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L
1
and 7 are not paralleled by a substantially higher kinase inhibition compared with indolobenzazepines L
4
and 11, arguing for additional targets and molecular effects, such as intercalation into DNA. 相似文献
4.
Seidel V Windhövel J Eaton G Alfermann AW Arroo RR Medarde M Petersen M Woolley JG 《Planta》2002,215(6):1031-1039
Cell cultures of Linum album Kotschy ex Boiss. (Linaceae) showing high accumulation of the lignan podophyllotoxin (PTOX) were established. Enzymological
studies revealed highest activities of phenylalanine ammonia-lyase, cinnamyl alcohol dehydrogenase, 4-hydroxycinnamate:CoA
ligase and cinnamoyl-CoA:NADP oxidoreductase immediately prior to PTOX accumulation. To investigate PTOX biosynthesis, feeding
experiments were performed with [2-13C]3′,4′-dimethoxycinnamic acid, [2-13C]3′,4′-methylenedioxycinnamic acid (MDCA), [2-13C]3′,4′,5′-trimethoxycinnamic acid, [2-13C]sinapic acid, [2-13C]- and [2,3-13C2]ferulic acid. Analysis of the metabolites by HPLC coupled to tandem mass spectrometry revealed incorporation of label from
ferulic acid into PTOX and deoxypodophyllotoxin (DOP). In addition, MDCA was also unambiguously incorporated intact into PTOX.
These observations suggest that in L. album both ferulic acid and methylenedioxy-substituted cinnamic acid can be incorporated into lignans. Furthermore, it appears
that, in this species, the hydroxylation of DOP is a rate-limiting point in the pathway leading to PTOX.
Electronic supplementary material to this article is available at and is accessible for authorized users.
Electronic Publication 相似文献
5.
P. Franchetti L. Messini L. Cappellacci G. Abu Sheikha M. Grifantini P. Guarracino 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1739-1755
Abstract 2′,3′-Dideoxy-8-aza-1-deazaadenosine (21) and its α-anomer (20) were synthesized via glycosylation of 7-chloro-3H-1,2,3-triazolo[4,5-b]pyridi-ne with 2,3-dideoxy-5-O-[(1, 1)-dimethylethyl)diphenylsilyl]-D-glycero-o-pen-tofuranosyl chloride. The reaction gave a mixture of α- and β-anomers of N3-, N4- and N1-glycosylated regioisorners (12–15). The α- and β-anomers of the N4-glycosylated isomer 26 and 27 were also synthesized through the glycosylation of 8-aza-1-deazaadenine with 1-acetoxy-2,3-dideoxy-5-O-f(1,1-di-methylethyl)dimethylsilyl]-D-glycero-pentouranose. These dideoxynucleo-sides and a series of previously synthesized 8-aza-1-deazapurine nucleosidcs were tested for activity against several DNA and RNA viruses, HIV-1 included. The α- and β-anomers of 7-chloro-3-(2-deoxy-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-b]pyridine (3a and 4) showed activities against Sb-1 and Coxs viruses. The α- and β-anomers of 2′,3′-dideoxy-8-aza-1-deazaadenosine (20 and 21) were found active as inhibitors of adenosine deaminase. 相似文献
6.
John L. Lewin David E. Heppner Christopher J. Cramer 《Journal of biological inorganic chemistry》2007,12(8):1221-1234
The bis(μ-oxo)/μ-η2:η2-peroxo equilibria for seven supported Cu2O2 cores were studied with different hybrid and nonhybrid density functional theory models, namely, BLYP, mPWPW, TPSS, TPSSh,
B3LYP, mPW1PW, and MPW1K. Supporting ligands 3,3′-iminobis(N,N-dimethylpropylamine), N,N,N′,N′,N″-pentamethyldipropylenetriamine, N-[2-(pyridin-2-yl)ethyl]-N,N,N′-trimethylpropane-1,3-diamine, bis[2-(2-pyridin-2-yl)ethyl]methylamine, bis[2-(4-methoxy-2-pyridin-2-yl)ethyl]methylamine,
bis[2-(4-N,N-dimethylamino-2-pyridin-2-yl)ethyl]methylamine, and 1,4,7-triisopropyl-1,4,7-triazacyclononane were chosen on the basis of
the availability of experimental data for comparison. Density functionals were examined with respect to their ability accurately
to reproduce experimental properties, including, in particular, geometries and relative energies for the bis(μ-oxo) and side-on
peroxo forms. While geometries from both hybrid and nonhybrid functionals were in good agreement with experiment, the incorporation
of Hartree–Fock (HF) exchange in hybrid density functionals was found to have a large, degrading effect on predicted relative
isomer energies. Specifically, hybrid functionals predicted the μ-η2:η2-peroxo isomer to be too stable by roughly 5–10 kcal mol−1 for each 10% of HF exchange incorporated into the model. Continuum solvation calculations predict electrostatic effects to
favor bis(μ-oxo) isomers by 1–4 kcal mol−1 depending on ligand size, with larger ligands having smaller differential solvation effects. Analysis of computed molecular
partition functions suggests that nonzero measured entropies of isomerization are likely to be primarily associated with interactions
between molecular solutes and their first solvation shell.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
7.
Mingzhang Gao Min Wang Qi-Huang Zheng 《Bioorganic & medicinal chemistry letters》2018,28(13):2234-2238
The reference standards methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate (5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide (5c), and their corresponding desmethylated precursors 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoic acid (6a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-hydroxybenzamide (6b), were synthesized from 5-amino-2,2-difluoro-1,3-benzodioxole and 3-substituted benzoic acids in 5 and 6 steps with 33% and 11%, 30% and 7% overall chemical yield, respectively. Carbon-11-labeled casein kinase 1 (CK1) inhibitors, [11C]methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate ([11C]5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-[11C]methoxybenzamide ([11C]5c), were prepared from their O-desmethylated precursor 6a or 6b with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 40–45% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740?GBq/μmol with a total synthesis time of ~40-min from EOB. 相似文献
8.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):968-973
In this work, we reported the synthesis and evaluation of antibacterial and antifungal activities of three new compound series obtained from 6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide: 2-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl}-N-alkyl/arylhydrazinecarbothioamides (2a–d), 4-alkyl/aryl-2,4-dihydro-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-3H-1,2,4-triazole-3-thiones (3a–n), and 2-alkyl/arylamino-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-1,3,4-thiadiazoles (4a–g). The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR (APT), mass and elemental analysis. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Candida albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, Trichophyton mentagrophytes var. erinacei NCPF 375, Microsporum gypseum NCPF 580, and T. tonsurans NCPF 245. 3c, 3f, 3m, 3n, and 4e showed the highest antibacterial activity. Particularly 3c, 3f, 3g, 3k, 3n, 4a, 4e, and 4g showed the highest antifungal activity against tested fungi. 相似文献
9.
Wiesława Bylka 《Acta Physiologiae Plantarum》2004,26(4):393-398
A new acetylated flavonol glycoside: patuletin 3-O-[5′″-O-feruloyl-β-D-apiofuransyl (1′″→2′′)-β-D-glucopyranoside] (2), together with a known patuletin 3-O-β-D-glucopyranoside (1) were isolated from the aerial part of Artiplex littoralis L. (Chenopodiacease). Their structures were elcidated by acid hydrolysis and spectroscopic methods including UV, 1H, 13C NMR and ESI-MS for both compounds, additionally 2D-NMR, HSQC, HMBC experiments were performed for 2. 相似文献
10.
Tun-Cheng Chien David A. Berry John C. Drach Leroy B. Townsend 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1971-1996
3-Amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl-4-(1,2,4-oxadiazol-3-yl)imidaz-oles (6a-d), with different substituents at the 5-position of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose, 3). It was found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)imidazole (6a) underwent the MHR with sodium hydride in DMF or DMSO to afford the corresponding 3-acetamidoimidazo[4,5-c]pyrazole nucleoside(s) (7b and/or 7a) in good yields. A direct removal of the acetyl group from 3-acetamidoimidazo[4,5-c]pyrazoles under numerous conditions was unsuccessful. Subsequent protecting group manipulations afforded the desired 3-amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) as a 5:5 fused analog of adenosine (1). 相似文献
11.
Ji-Yong Liu Hai-Ling Yu Zhe-Shan Quan Xun Cui Hu-Ri Piao 《Bioorganic & medicinal chemistry letters》2009,19(9):2392-2395
A series of 1-substituted-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl) piperidine-4-carboxamides has been synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit-heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 1-(2-fluorobenzyl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)piperidine-4-carboxamide 6a was the most potent, increasing stroke volume by 11.92 ± 0.35% (milrinone: 6.36 ± 0.13%) at 1 × 10?4 M. 相似文献
12.
The synthesis and X-ray structures of copper(II) complexes of the bidentate ligands, N-(4-oxo-5,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-N′-phenylguanidino, 2-uanidinobenzimidazolo and N-(4-oxo-3-phenyl-1,3-diazaspiro[4.4]non-1-en-2-yl)guanidino, are reported. These complexes, which possess potential doublet (DA) or triplet (DAD) hydrogen bonding motifs, can form supramolecular structures based on synthons involving hydrogen bonding or phenyl embraces. The changes in supramolecular structure resulting from small changes in ligand structure, as well as from the use of different solvents for their crystallisation, are examined. The structures adopted are compared with others reported previously for complexes of related ligands. 相似文献
13.
Siragusa M Carra A Salvia L Puglia AM De Pasquale F Carimi F 《Plant cell reports》2007,26(8):1289-1296
Somatic embryos were regenerated in vitro from calamondin style–stigma explants cultured in the presence of N
6-benzylaminopurine (BAP) cytokinin and three synthetic phenylurea derivatives, N-(2-chloro-4-pyridyl)-N-phenylurea (4-CPPU), N-phenyl-N′-benzothiazol-6-ylurea (PBU) and N,N′-bis-(2,3-methilendioxyphenyl)urea (2,3-MDPU). The phenylurea derivative compounds tested at micromolar level (12 μM) were
able to induce a percentage of responsive explants significantly higher from that obtained with BAP and hormone-free (HF)
conditions. In order to verify the genetic stability of the regenerants, 27 plants coming from different embryogenic events
were randomly selected from each different culture condition and evaluated for somaclonal variations using inter-simple sequence
repeat and random amplified polymorphic DNA analyses. We observed that 2,3-MDPU and PBU gave 3.7% of somaclonal mutants, whereas
4-CPPU gave 7.4% of mutants. No somaclonal variability was observed when plantlets were regenerated in BAP or HF medium. Although
diphenylurea derivatives show a higher embryogenic potential as compared to BAP, they induce higher levels of somaclonal variability.
This finding should be taken in consideration when new protocols for clonal propagation are being developed. 相似文献
14.
M. A. Ivanov G. S. Ludva A. V. Mukovnya S. N. Kochetkov V. L. Tunitskaya L. A. Alexandrova 《Russian Journal of Bioorganic Chemistry》2010,36(4):488-496
4′-Fluoro-2′,3′-O-isopropylidenecytidine was synthesized by the treatment of 5′-O-acetyl-4′-fluoro-2′,3′-O-isopropylideneuridine with triazole and 4-chlorophenyl dichlorophosphate followed by ammonolysis. The interaction of 4′-fluoro-2′,3′-O-isopropylidenecytidine with hydroxylamine resulted in 4′-fluoro-2′,3′-O-isopropylidene-5′-O-acetyl-N
4-hydroxycytidine. The removal of the 2′,3′-O-isopropylidene groups led to acetyl derivatives of 4′-fluorouridine, 4′-fluorocytidine, and 4′-fluoro-N
4-hydroxycytidine. 4′-Fluorouridine 5′-O-triphosphate was obtained in three steps starting from 4′-fluoro-2′,3′-O-isopropylideneuridine. 4′-Fluorouridine 5′-O-triphosphate was shown to be an effective inhibitor of HCV RNA-dependent RNA polymerase and a substrate for the NTPase reaction
catalyzed by the HCV NS3 protein, the hydrolysis rate being similar to that of ATP. It could also activate a helicase reaction
with an efficacy of only threefold lower than that for ATP. 相似文献
15.
Ahmed A. Fayed Abd El-Galil E. Amr Mohamed A. Al-Omar Elsayed E. Mostafa 《Russian Journal of Bioorganic Chemistry》2014,40(3):308-313
A series of new 3-substituted-7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives were synthesized as antimicrobial agents using 7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methyl-4H-pyrido[3′,2′:4,5]thieno[3,2-d]-[1,3]oxazin-4-one as a starting compound. Its condensation with substituted aniline derivatives or phenyl hydrazine gave the corresponding N-substituted derivatives. Treatment of the starting compound with hydrazine hydrate afforded the corresponding N-amino derivative, which was reacted with substituted phenylisocyanate and phenylisothiocyanate derivatives to give the corresponding semicarbazides and thiosemicarbazide derivatives. All the newly synthesized compounds were evaluated for their antimicrobial activities in comparison to streptomycin and fusidic acid as positive controls. The structure assignments of the new compounds are based on chemical and spectroscopic evidence. 相似文献
16.
Mark A. Sprecker Alan G. Morrice Bruce A. Gruber Nelson J. Leonard Ruth Y. Schmitz Folke Skoog 《Phytochemistry》1976,15(5):609-613
We have synthesized and compared the cytokinin activities in the tobacco bioassay of a series of benzologs of 6-(3-methyl-2-butenylamino)purine (N6-(Δ2-isopentenyl)adenine) (1a) and 6-benzylaminopurine (N6-benzyl-adenine) (1c). The linear benzo analogs 8-(3-methyl-2-butenylamino)imidazo[4,5-g]quinazoline (2b) and 8-benzyla-minoimidazo[4,5-g]quinazoline (2c) are active, while 9-(3-methyl-2-butenylamino)imidazo[4,5-f]quinazoline (3b) and 6-(3-methyl-2-butenylamino)imidazo[4,5-h]quinazoline (4b) are slightly active and 9-benzylaminoimidazo[4,5-f]-quinazoline (3c) and 6-benzylaminoimidazo[4,5-h]quinazoline (4c) are inactive. Compounds 2b and 2c represent the first examples of active cytokinins containing a tri-heterocyclic moiety. The above series of compounds demonstrates structural factors that affect cytokinin activity. These compounds also have interesting fluorescence properties which could render them useful as probes to study the mechanism of cytokinin action. 相似文献
17.
SUMMARY 1. The serotonin1A receptors are members of a superfamily of seven transmembrane domain receptors that couple to G-proteins, and appear to be involved in several behavioral and cognitive functions.2. We monitored the effect of prolonged treatment of the human serotonin1A receptor expressed in Chinese hamster ovary (CHO) cells with pharmacologically well-characterized ligands on its binding to the agonist 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) and antagonist 4-(2′-methoxy)-phenyl-1-[2′-(N-2″-pyridinyl)-p-fluorodobenzamido]ethyl-piperazine (p-MPPF).3. Our results indicate that prolonged treatment with the specific agonist (8-OH-DPAT) differentially affects subsequent binding of the agonist and antagonist to the receptor in a manner independent of receptor-G-protein coupling. Importantly, our results show that prolonged treatment with the commonly used antagonist p-MPPF, and its iodinated analogue 4-(2′-methoxy)-phenyl-1-[2′-(N-2″-pyridinyl)-p-iodobenzamido]ethyl-piperazine (p-MPPI), which have earlier been reported to display similar binding properties to serotonin1A receptors, induces significantly different effects on the ligand binding function of serotonin1A receptors. 相似文献
18.
Vasanthakumar P. Rajappan Ramachandra S. Hosmane 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1141-1151
Abstract Synthesis and biochemical screening against guanase of analogues of the naturally occurring guanase inhibitor azepinomycin (2) are reported. Compound e-amino-5,6,7,8,-tetrahydro-4H-imidazo[4,5-e][1,4]diazepine-5,8-dione (3) was synthesized in six steps commencing with 1-benzyl-5-nitroimidazole-4-carboxylic acid (5). Compound 3 and its synthetic precursor 3-benzyl-6-(N-benzyloxycarbonyl)amino-5,6,7,8-tetrahydro-4H-imidazo[4,5-e][1,4]diazepine-5,8-dione (12) were screened against rabbit liver guanase. Both were found to be moderate inhibitors of the enzyme with K1′s in the range of 10?4 M. 相似文献
19.
The present model study explores the chemistry of methionine complexes and ternary methionine-guanine adducts formed by trans-[PtCl2(NH3)2] (1) and antitumor trans-[PtCl2(NH3)quinoline] (2) using 1D (1H, 195Pt) and 2D NMR spectroscopy. Compound 2 was substitution inert in reactions with N-acetyl-lmethionine [AcMet(H)]. Reactions of trans-[PtCl(NO3)(NH3)quinoline] (5) ("monoactivated" 2) with AcMetH in water and acetone at various stoichiometries point to Pt(II)-S binding that requires prior activation of
the Pt-Cl bond by labile oxygen donors. Trans-[PtCl{AcMet(H)-S}(NH3)quinoline](NO3) (6) and trans-[Pt{AcMet(H)-S}2(NH3)quinoline](NO3)2 (7) were isolated from these mixtures. At high [Cl–], AcMet(H) is displaced from 7, giving 6. Frozen stereodynamics in 6 at the thioether-S and slow rotation about the Pt-Nquinoline bond result in four spectroscopically distinguishable diastereomers. 1H NMR spectra of 7 show faster exchange dynamics due to mutual trans-labilization of the sulfur donors. Substitution of chloride in trans-[PtCl(9-EtGua)(NH3)L]NO3 (L=NH3, 3; L=quinoline, 4; 9-EtGua=9-ethylguanine, which mimics the first DNA binding step of 1 and 2) by methionine-sulfur proceeded ca. 2.5 times slower for the quinoline compound. Both reactions, in turn, proved to be ca.
4 times faster than binding of a second nucleobase under analogous conditions. From the resulting mixtures the ternary adducts
trans-[Pt(AcMet-S)(9-EtGua-N7)(NH3)L](NO3, Cl) (L=NH3, 8; L=quinoline, 9) were isolated. A species analogous to 9 formed in a rapid reaction between 6 and 5′-guanosine monophosphate (5′-GMP). From NMR data an AMBER-based solution structure of the resulting adduct, trans-[Pt(AcMet-S)(5′-GMP-N7)(NH3)quinoline] (10), was derived. The unusual reactivity along the N7-Pt-S axis in 8–10 resulted in partial release of both 9-EtGua and AcMet at high [Cl–]. Possible consequences of the kinetic and structural effects (e.g., trans effect of sulfur, steric demand of quinoline) observed in these systems with respect to the (trans)formation of potential
biological cross-links are discussed.
Received: 25 May 1998 / Accepted: 6 August 1998 相似文献
20.
A UDP-glucose: anthocyanin 3′,5′-O-glucosyltransferase (UA3′5′GT) (EC 2.4.1.-) was purified from the petals of Clitoria ternatea L. (Phaseoleae), which accumulate polyacylated anthocyanins named ternatins. In the biosynthesis of ternatins, delphinidin
3-O-(6″-O-malonyl)-β-glucoside (1) is first converted to delphinidin 3-O-(6″-O-malonyl)-β-glucoside-3′-O-β-glucoside (2). Then 2 is converted to ternatin C5 (3), which is delphinidin 3-O-(6″-O-malonyl)-β-glucoside-3′,5′-di-O-β-glucoside. UA3′5′GT is responsible for these two steps by transferring two glucosyl groups in a stepwise manner. Its substrate
specificity revealed the regioselectivity to the anthocyanin′s 3′- or 5′-OH groups. Its kinetic properties showed comparable
k
cat values for 1 and 2, suggesting the subequality of these anthocyanins as substrates. However, the apparent K
m value for 1 (3.89 × 10−5 M), which is lower than that for 2 (1.38 × 10−4 M), renders the k
cat/K
m value for 1 smaller, making 1 catalytically more efficient than 2. Although the apparent K
m value for UDP-glucose (6.18 × 10−3 M) with saturated 2 is larger than that for UDP-glucose (1.49 × 10−3 M) with saturated 1, the k
cat values are almost the same, suggesting the UDP-glucose binding inhibition by 2 as a product. UA3′5′GT turns the product 2 into a substrate possibly by reversing the B-ring of 2 along the C2-C1′ single bond axis so that the 5′-OH group of 2 can point toward the catalytic center.
K. Kogawa, N. Kato, K. Kazuma, and N. Noda contributed equally to this work. 相似文献