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1.
The total syntheses of hypomurocin A3 and hypomuricin A5 (HM A3 and HM A5, resp.) in solution phase are described. These syntheses have been successfully achieved by applying the ‘azirine/oxazolone method’ to introduce the two Aib‐Pro units into the backbone of these undecapeptaibols in one step with methyl 2,2‐dimethyl‐2H‐azirine‐3‐prolinate as the ‘Aib‐Pro synthon’. The coupling of Z‐protected (Z=(benzyloxy)carbonyl) amino acids or peptide acids with amino acid tert‐butyl esters and of peptide segments was carried out according to the TBTU (=O‐(benzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium tetrafluoroborate) and HOBt (=1‐hydroxybenzotriazole) protocol. Purification by reversed‐phase HPLC gave the peptides in pure form. The products were characterized by optical rotation, NMR and IR spectroscopy, mass spectrometry, and elemental analysis. The crystal structures of HM A3 and of an octapeptide fragment of HM A5 could be obtained. An NMR analysis was also carried out with HM A3 and HM A5 to determine their conformations in solution. A global structural comparison between the three sequences of HM A1, HM A3, and HM A5 was performed, as well as the HPLC correlation of the natural HM A family and the synthetic samples. 相似文献
2.
In the preceding paper in this issue, we reported the total syntheses in solution of a set of four TOAC-containing analogues of the [L-Glu(OMe)(7,18,19)] F50/5 component of alamethicin, the prototype of peptaibol antibiotics forming channels in the biological membranes. In this article, we have expanded this work to the examination of their preferred conformation in solution by use of a combination of CD, FT-IR absorption, and NMR spectroscopies. The results are strongly in favor of the view that replacement of the Aib residues at positions 1, 8, and 16 with TOAC (both are members of the helicogenic sub-class of C(alpha)-tetrasubstituted alpha-amino acids) does not significantly affect the overwhelmingly populated alpha-helical 3D structure of alamethicin. The X-ray diffraction crystal structure of the N(alpha)-protected, C-terminal, hexapeptide amide segment Z-L-Pro-L-Val-(Aib)(2)-[L-Glu(OMe)](2)-Fol lends further support to our conformational conclusions. 相似文献
3.
Mijovilovich A 《化学与生物多样性》2008,5(10):2131-2139
The 2-His-1-carboxylate triad is an Fe(II)-binding motif common to several enzyme families. Within the catalytic cycle, the metal ion seems to alter between hexa- and pentacoordination, providing an open space in the Fe moiety for dioxygen binding. Anyhow, based on crystallographic studies, the picture is not fully consistent as different coordination numbers are reported for similar states. Moreover, the orientation of the metal-coordinating carboxylate varies in these studies. These differences are reflected in the XANES spectra analyzed in this paper. For isolated tyrosine and phenylalanine hydroxylase, the different active-site structures postulated by protein crystallography and further improved using spectroscopic data result in calculated XANES pattern that resemble very well the experiments. This work shows that structural differences in the non-coordinated oxygen of the carboxylate have no effect in the EXAFS but cause a change in the white-line intensity that can be successfully modeled within the muffin-tin approximation in small clusters. Thus, the study shows a way to analyze the 'carboxylate shift'. This highlights the potential of XANES analysis and clearly shows that the mentioned structural differences are present in solution as well, and does neither reflect the crystallization artifacts nor result from radiation damage or lacking resolution. 相似文献
4.
Three structurally different types of small peptides, namely, i) Boc‐Ile‐Aib‐Ile‐OMe (Aib=α‐aminoisobutyric acid), ii) Boc‐Xx‐m‐aminobenzoic acid (Xx=β‐Ala and γ‐aminobutyric acid), and iii) Boc‐Xx‐m‐nitroaniline, were found to exhibit β‐sheet‐mediated fibrillogenesis in the solid state, revealed by FT‐IR, single‐crystal X‐ray diffraction, and FE‐SEM studies. Interestingly, the fibrils grown from peptides 2 and 3 were found to bind with the physiological dye Congo red, a characteristic feature of amyloid fibrils. 相似文献
5.
Ten limonoids, named granatumins L–U ( 1 – 10 , resp.), were isolated from the seeds of an Indian mangrove, Xylocarpus granatum, collected in the estuary of Krishna, Andhra Pradesh. The structures of these compounds were established on the basis of spectroscopic data. The relative configuration of granatumin L ( 1 ) was confirmed by a single‐crystal X‐ray diffraction analysis. Granatumins L–T ( 1 – 9 , resp.) belong to the small group of limonoids with an oxygen bridge between C(1) and C(29), while granatumin U ( 10 ) is a 28‐Me‐oxidized mexicanolide. This is the first report of limonoids with an O‐bridge between C(1) and C(29) from the Indian X. granatum. The pronounced structural diversity of limonoids from this mangrove might originate from environmental factors. 相似文献
6.
de Oliveira SL Tavares JF Branco MV Lucena HF Barbosa-Filho JM de F Agra M do Nascimento SC dos S Aguiar J da Silva TG de Simone CA de Araújo-Júnior JX da Silva MS 《化学与生物多样性》2011,8(1):155-165
Three tropane alkaloids, 1-3, were isolated from Erythroxylum caatingae, i.e., 6β-benzoyloxy-3α-[(4-hydroxy-3,5-dimethoxybenzoyl)oxy]tropane (1), a new tropane alkaloid, along with the known alkaloids 3α,6β-dibenzoyloxytropane (2) and 6β-benzoyloxy-3α-[(3,4,5-trimethoxybenzoyl)oxy]tropane (catuabine B; 3). Their structures were determined by 2D- ((1) H and (13) C) NMR. By LC/ESI-MS/MS analysis of the fractions of alkaloids 1-3, it was possible to detect five more alkaloids, 4-8, two of these, 4 and 8, possibly being new natural products. X-Ray crystallography of the chloride derivate of 1, i.e., 6β-benzoyloxy-3α-(4-hydroxy-3,5-dimethoxybenzoyloxy)tropane hydrochloride (1a) confirmed the structure of 1. Cytotoxicity was tested against the cell lines HEp-2, NCI-H292, and KB for the MeOH extract and alkaloid 3, and antitumor activity was tested against Sarcoma 180 only for the MeOH extract. 相似文献
7.
Aryl Hetaryl Ketones and Thioketones as Efficient Inhibitors of Peptidyl‐Prolyl cis‐trans Isomerases
Thomas Hediger Walter Frank Michael Schumann Gunter Fischer Manfred Braun 《化学与生物多样性》2012,9(11):2618-2634
A series of 18 differently substituted new aryl hetaryl ketones and thioketones were synthesized in four to six steps from commercial starting materials. The new ketones were evaluated as inhibitors of the peptidyl‐prolyl cis‐trans isomerase hPin1 with Ki values ranging in the one‐digit micromolar to sub‐micromolar numbers. A crystal structure revealed the non‐planar arrangement of the aryl residues at the carbonyl compound and supports the hypothesis that the new compounds might mimic the transition state of the enzymatic conversion. 相似文献
8.
Xiaoyu Wang Lianli Sun Kexin Huang Shuyun Shi Lijuan Zhang Juanhua Xu Hua Peng Xianfeng Sun Liwei Wang Xiumei Wu Yu Zhao Xiaokun Li Joachim Stöckigt Jia Qu 《化学与生物多样性》2009,6(7):1053-1065
A phytochemical investigation of the roots of Ligularia atroviolacea resulted in the isolation of 24 compounds including seven new eremophilanoids named eremophila‐3,7(11),8‐triene‐12,8;14,6α‐diolide ( 1 ), 3β‐(angeloyloxy)eremophil‐7(11)‐en‐12,8β‐olid‐14‐oic acid ( 2 ), 1α‐chloro‐10β‐hydroxy‐6β‐(2‐methylpropanoyloxy)‐9‐oxo‐7,8‐furoeremophilane ( 3 ), (10βH)‐8‐oxoeremophila‐3(4),6(7)‐diene‐12,14‐dioic acid ( 4 ), (10αH)‐8‐oxoeremophila‐3(4),6(7)‐diene‐12,14‐dioic acid ( 5 ), 8β‐[eremophila‐3′,7′(11′)‐diene‐12′,8′α;14′,6′α‐diolide]eremophila‐3,7(11)‐diene‐12,8α;14,6α‐diolide ( 6 ), and ligulatrovine A ( 7 ), eleven known eremophilanoids, 8 – 18 , four steroids, one glucose derivative, and one fatty acid. The structures of these compounds were elucidated by spectroscopic methods including 2D‐NMR experiments. The structure of 3 was also established by an X‐ray diffraction study. The in vitro cytotoxicity evaluation of selected compounds was performed on seven cultured tumor cell lines, i.e., KB, BEL‐7404, A549, HL‐60, HeLa, CNE, and P‐388D1. The preliminary taxonomy of this species was also discussed, and the possible biogenesis of a dimer possessing a new noreremophilanoid type skeleton, 7 , is presented in a preliminary form. 相似文献
9.
Trichoderma spp. are regularly found as a constituent of the mycoflora of many soils and are noted for their antagonistic activity against bacteria and other fungi. This latter property is the basis for the widespread interest in their use in the biological control of soil-borne fungal plant pathogens. This antagonism is partly based on their ability to produce an impressive inventory of secondary metabolites. An important group of bioactive metabolites produced by Trichoderma spp. are the non-ribosomal peptides (NRPs), especially the peptaibols. A virulent antagonistic strain, T. asperellum, which had been used in biological control strategies in Malaysia and previously examined for mycolytic enzyme production, has been studied for its potential for peptaibol production. The present research demonstrated the ability of T. asperellum to produce at least two metabolites which were identified as acid trichotoxin 1704E (Ac-Aib-Gly-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Ala-Ala-Aib-Pro-Leu-Aib-Iva-Glu-Vol) and neutral trichotoxin 1717A (Ac-Aib-Gly-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Ala-Aib-Aib-Pro-Leu-Aib-Iva-Gln-Vol). Addition of free Aib to the culture medium enhanced the production of trichotoxins. Biological activity of these substances was investigated against Bacillus stearothermophilus. The general characteristics of peptaibols, also found in the trichotoxins, include the presence of high proportions of the uncommon amino acid Aib, the protection of the N- and C-termini by an acetyl group and reduction of the C-terminus to 2-amino alcohols, respectively, amphipathy and microheterogeneity. 相似文献
10.
Three meta-dicopper complexes, 1-3, based on 5-substituted 1,3-xylylene spacer have been synthesized. These complexes are capable of inducing the transformation of supercoiled DNA (pUC19) to its nicked and linear DNA form in the presence of ascorbate, and their DNA nicking efficiency can be correlated to their DNA-binding ability. The cleavage mechanism is similar to that of the non-substituted meta-dicopper complex A. Amongst the three complexes, 5-(aminomethyl)-substituted complex 3 displayed a higher DNA-binding ability and nicking efficiency than unsubstituted complex A. The CD-spectroscopic study and structural analysis imply that the different CuCu distances and DNA binding modes induced by different 5-substituents on benzene-1,3-bis(methylene) spacer may be responsible for the different DNA cleaving behavior of meta-dicopper complexes. 相似文献
11.
Anna S. Gardberg Alexis Rae Del Castillo Kevin L. Weiss Flora Meilleur Matthew P. Blakeley Dean A. A. Myles 《Acta Crystallographica. Section D, Structural Biology》2010,66(5):558-567
The locations of H atoms in biological structures can be difficult to determine using X‐ray diffraction methods. Neutron diffraction offers a relatively greater scattering magnitude from H and D atoms. Here, 1.65 Å resolution neutron diffraction studies of fully perdeuterated and selectively CH3‐protonated perdeuterated crystals of Pyrococcus furiosus rubredoxin (D‐rubredoxin and HD‐rubredoxin, respectively) at room temperature (RT) are described, as well as 1.1 Å resolution X‐ray diffraction studies of the same protein at both RT and 100 K. The two techniques are quantitatively compared in terms of their power to directly provide atomic positions for D atoms and analyze the role played by atomic thermal motion by computing the σ level at the D‐atom coordinate in simulated‐annealing composite D‐OMIT maps. It is shown that 1.65 Å resolution RT neutron data for perdeuterated rubredoxin are ∼8 times more likely overall to provide high‐confidence positions for D atoms than 1.1 Å resolution X‐ray data at 100 K or RT. At or above the 1.0σ level, the joint X‐ray/neutron (XN) structures define 342/378 (90%) and 291/365 (80%) of the D‐atom positions for D‐rubredoxin and HD‐rubredoxin, respectively. The X‐ray‐only 1.1 Å resolution 100 K structures determine only 19/388 (5%) and 8/388 (2%) of the D‐atom positions above the 1.0σ level for D‐rubredoxin and HD‐rubredoxin, respectively. Furthermore, the improved model obtained from joint XN refinement yielded improved electron‐density maps, permitting the location of more D atoms than electron‐density maps from models refined against X‐ray data only. 相似文献
12.
Selenium (Se) can provide unique biochemical and biological functions, and properties to macromolecules, including protein and RNA. Although Se has not yet been found in DNA, identification of the presence of Se in natural tRNAs has led to discovery of the naturally occurring 2-selenouridine and 5-[(methylamino)methyl]-2-selenouridine (mnm(5)se(2)U). The Se-atoms at C(2) of the modified uridines are introduced by 2-selenouridine synthase via displacement of the S-atoms in the corresponding 2-thiouridine nucleotides of the tRNAs, and selenophosphate is used as the Se donor. The research indicated that mnm(5)se(2)U is located at the first or wobble position of the anticodons in several bacterial tRNAs, including tRNA(Lys), tRNA(Glu), and tRNA(Gln). The 2-seleno functionality on this modified nucleotide probably improves the translation accuracy and/or efficiency. These observations in vivo suggest that the presence of Se can provide natural RNAs with useful properties to better function and survival. To further investigate the biochemical and structural properties of Se-derivatized nucleic acids (SeNA), we have pioneered chemical and enzymatic synthesis of Se-derivatized nucleic acids, and introduced Se into both RNA and DNA at a variety of positions by atom-specific replacement of oxygen. This review outlines the recent advancements in chemical and biochemical syntheses, and studies of SeNAs, and their potential applications in structural and functional investigation of nucleic acids and their protein complexes. 相似文献
13.
Two coriamyrtin-type sesquiterpenes, fengfangin A (1) and tutin (2), and six diarylheptanoids, namely alnusone (3), centrolobol (4), muricarpone B (5), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptan-3-one (6), (3S)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptan-3-ol (7), and (3S)-1-(4-hydroxyphenyl)-7-(3,4-dihydroxyphenyl)heptan-3-ol (8), were isolated from the 95% EtOH extract of nidus vespae, the nest of Polistes species. Their structures were identified by spectroscopic methods. Compounds 1 and 8 are new products. The absolute configuration of 1 was determined by single-crystal X-ray diffraction analysis using Flack parameter. The biological tests showed that compounds 5, 6, and 8 could inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with IC(50) values in the range of 13-17 μM, whereas the sesquiterpenes were inactive in this assay (>25 μM). In addition, the ecological significance of the presence of neurotoxic sesquiterpene lactones in nidus vespae is briefly discussed. 相似文献
14.
Vanadate-dependent peroxidases contain, in their active center, vanadate covalently attached to histidine in an overall trigonal-bipyramidal array. We describe here the synthesis and characterization of optically active amino alcohols and their vanadium(V) complexes, and we show that the structural models of the active center thus obtained are also functional models for the sulfide-peroxidase activity of the enzyme in heterogeneous catalysis. The heterogeneous systems were obtained by immobilizing the complexes on silica gel and mesoporous silicas, and by aggregation. The following ligands, ligand precursors, and V compounds have been structurally characterized: (R)-(2-phenylethanol)-(R)-1-phenylethylamine (HL(A)), (R,R)-bis[2-phenyl(ethylmethylether)]ammonium chloride ([L(D)]+Cl(-)), the carbasilatranes (R,R)-methoxy{N,N',N'-2,2',3-[bis(1-phenylethanolato)propyl]amino}silane ((R,R)-Si(OMe)L(E)), (R,R)-methoxy-{N,N',N'-1,2',3-[(1-phenylethanolato)-(2-phenylethanolato)propyl]amino}silane ((R,R)-Si(OMe)L(E')), and [VO(L(F))(OSiMe2(t)Bu)], where H2L(F)=ethylbis(2-hydroxy-2-phenylethyl)amine. 相似文献
15.
Akifumi Higashiura Takeshi Kurakane Makoto Matsuda Mamoru Suzuki Koji Inaka Masaru Sato Tomoyuki Kobayashi Tetsuo Tanaka Hiroaki Tanaka Kazuko Fujiwara Atsushi Nakagawa 《Acta Crystallographica. Section D, Structural Biology》2010,66(6):698-708
Recent technical improvements in macromolecular X‐ray crystallography have significantly improved the resolution limit of protein structures. However, examples of high‐resolution structure determination are still limited. In this study, the X‐ray crystal structure of bovine H‐protein, a component of the glycine cleavage system, was determined at 0.88 Å resolution. This is the first ultrahigh‐resolution structure of an H‐protein. The data were collected using synchrotron radiation. Because of limitations of the hardware, especially the dynamic range of the CCD detector, three data sets (high‐, medium‐ and low‐resolution data sets) were measured in order to obtain a complete set of data. To improve the quality of the merged data, the reference data set was optimized for merging and the merged data were assessed by comparing merging statistics and R factors against the final model and the number of visualized H atoms. In addition, the advantages of merging three data sets were evaluated. The omission of low‐resolution reflections had an adverse effect on visualization of H atoms in hydrogen‐omit maps. Visualization of hydrogen electron density is a good indicator for assessing the quality of high‐resolution X‐ray diffraction data. 相似文献
16.
Hucheng Zhu Chunmei Chen Jianping Wang Xiao‐Nian Li Guangzheng Wei Yi Guo Guangmin Yao Zengwei Luo Jinwen Zhang Yongbo Xue Yonghui Zhang 《化学与生物多样性》2015,12(10):1547-1553
A highly oxygenated hexacyclic indole alkaloid, penicamedine A ( 1 ), bearing a rare furan ring, was isolated from the culture broth of Penicillium camemberti, together with two known analogs, iso‐α‐cyclopiazonic acid ( 2 ) and cyclopiazonic acid ( 3 ). The structure of 1 was elucidated by comprehensive spectroscopic analyses including NMR and HR‐ESI‐MS. Its absolute configuration was further confirmed unambiguously by single‐crystal X‐ray diffraction analysis. Compound 1 was evaluated for anti‐HIV activity with p24 assays and tested for cytotoxic activities against five human cancer cell lines, including HL‐60, SMMC‐7721, A‐549, MCF‐7, SW480, and the immortalized non‐cancerous human pulmonary epithelial cell line BEAS‐2B by MTS method. 相似文献
17.
18.
Triana J López M Pérez FJ León F Quintana J Estévez F Hernández JC González-Platas J Brouard I Bermejo J 《化学与生物多样性》2011,8(11):2080-2089
Two new compounds, the sesquiterpene (1E,5E)-8β-acetoxy-4α-hydroxy-7βH-germacra-1(10),5-dien-14-oic acid (2), and a nor-sesquiterpene, (5E)-8β-acetoxy-4α-hydroxy-7βH-germacr-5-en-10-one (3), were isolated from Pulicaria canariensis ssp. lanata, along with ten known compounds, including the flavonoid 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (4). From Pulicaria burchardii, we isolated seven known compounds; the physical and spectroscopic data of the triterpenoid 3β-hydroxytaraxaster-20-en-30-al (1) are reported. The structures of compounds 1-3 were determined on the basis of HR-MS, and 1D- and 2D-NMR studies. The structure of 2 was corroborated by X-ray crystal diffraction. Cell viability experiments revealed that the semisynthetic flavonoid 4b was the most cytotoxic compound against human leukemia cells, and the cytotoxicity was caused by induction of apoptosis, as determined by microscopy of nuclear changes. 相似文献
19.
The clerodane diterpenoid salvinorin A (1), the main active component of the psychotropic herb Salvia divinorum, has been reported to be a potent agonist at the kappa-opioid receptor. Computer modeling suggested that splendidin (2) from S. splendens, as well as related compounds, might possess similar activities. In the present study, this hypothesis was tested by determination of the binding properties of a series of structural congeners, compounds 2-8, at the mu-, delta-, and kappa-opioid receptors. However, none of these compounds showed significant binding to any of the opioid-receptor subtypes, thus disproving the above hypothesis. The novel compounds 7 and 8 were obtained semi-synthetically by selective modification of salvifarin (5), isolated from Salvia farinacea, upon epoxide-ring opening with AcOH in the presence of indium(III) triflate. Also, the X-ray crystal structure of salvifaricin (6; Fig.), obtained from S. farinacea, was determined for the first time and used, in combination with in-depth NMR experiments, to elucidate the absolute configurations of the new products. Our experiments demonstrate that the relatively well-accessible diterpenoid 6 could be used as starting material for future studies into the structure-activity relationship at the kappa-opioid receptor. 相似文献
20.
A phytochemical investigation of the branches and leaves of Cephalotaxus lanceolata resulted in the isolation of three new cephalotaxus alkaloids, cephalancetines A, B, and D ( 1, 2 , and 4 , resp.), together with ten known alkaloids, 3 and 5 – 13 . The structures of the alkaloids were elucidated on the basis of spectroscopic analyses, including 1D‐ and 2D‐NMR, and HR‐ESI‐MS, and single‐crystal X‐ray diffraction. All isolated compounds were tested for their cytotoxicities against four human tumor cell lines, A549, HCT116, SK‐BR‐3, and HepG2. Compounds 12 and 13 showed remarkable activities against A549, HCT116, and HepG2 cell lines. 相似文献