Sugar-amide surfactant micelles as effective reaction fields for enantioselective hydrolysis of alpha-amino acid esters

The enantioselective hydrolysis of p-nitrophenyl esters of alpha-amino acids (Phe, Leu, Ala) was accomplished in micelles formed with the surfactants bearing one or two sugar-amide headgroups. The effect of structural variations in such sugar-amide surfactants on the rates and enantioselectivity (kD/kL) for hydrolysis of p-nitrophenyl esters of D- and L-phenylalanine hydrogen bromides (D- and L-PheONp) was studied. Both the hydrolysis rate of D-PheONp and the enantioselectivity increased with an increase in the alkyl chain length as well as an increase in the number of the alkyl chains in the maltobionamide-type surfactants. Enantioselectivity also increased with an increase in the sugar chain length from bisgluconamide to bismaltobionamide (by one glucose unit per each sugar chain) in the double-sugar-chain surfactants, but enantioselectivity was no longer influenced by a further increase to bismaltotrionamide. The stereochemistry of the linkage between the sugar units in the sugar chain remarkably affected the enantioselectivity: the maltobionamide-type surfactant, in which the two sugar units are connected by an alpha-1,4-glucosidic linkage, showed high enantioselectivity (kD/kL = 5.5), whereas the surfactant bearing cellobionamide headgroups (beta-1,4-glucosidic linkage) showed no enantioselectivity. Similar trends were observed when p-nitrophenyl esters of D- and L-leucine hydrogen bromides were used as substrates. On the other hand, the rates and enantioselectivity for hydrolysis of p-nitrophenyl esters of D- and L-alanine hydrogen bromides were not so largely affected by the structural variations in the sugar-amide surfactants. Additionally, the effects of the surfactant concentration and the reaction temperature on the rates and enantioselectivity for the hydrolysis of D- and L-PheONp were examined.     

The resin glycosides from the sweet potato (Ipomoea batatas L. LAM.)

Four new and two known ether-soluble resin glycosides were isolated from popular sweet potato (the roots of Ipomoea batatas L. LAM., Kokei 14 go, Convolvulaceae) in Japan. Unlike ester-type dimers, batatins I and II, obtained from other sweet potato (Ipomoea batabas var. batatas), the glycosides were tetra or pentasaccharide monomers in which the sugar moieties are partially acylated by organic acids and combine with the aglycone, jalapinolic acid, to form a macrocyclic ester.     

Structural characterization of pregnane glycosides from Cynanchum auriculatum by liquid chromatography on a hybrid ion trap time‐of‐flight mass spectrometer

A method coupling high‐performance liquid chromatography with hybrid ion trap time‐of‐flight mass spectrometry (TOFMS) using an electrospray ionization source was firstly used to characterize ten major pregnane glycosides including one novel compound auriculoside IV from the roots of Cynanchum auriculatum Royle ex Wight. In the MS/MS spectra, fragmentation reactions of the [M+Na]⁺ were recorded to provide abundant structural information on the aglycone and glycosyl moieties. Experiments using TOFMS allowed us to obtain precise elemental compositions of molecular ions and subsequent product ions with errors less than 6 ppm. The pregnane glycosides in C. auriculatum were classified into two major core groups: one is caudatin characterized by the neutral loss of one ikemamic acid molecule (128 Da) from the precursor ion, and the other is kidjoranin characterized by the neutral loss of cinnamic acid (148 Da) from the precursor ion. Meanwhile, a series of sugar‐chain fragment ions provided valuable information about the compositions of the sugar residues and the sequences of the sugar chain. Logical fragmentation pathways for pregnane glycosides have been proposed and are useful for the identification of these compounds in natural products especially when there are no reference compounds available. Copyright © 2009 John Wiley & Sons, Ltd.     

CHAIN BREAKAGE ACCOMPANYING THE PHOTOLYSIS OF IdUrd-DNA

Abstract DNA isolated from Escherichia coli and substituted with various amounts of iododeoxyuridine (12-95%) was irradiated at either 265. 300 or 313 nm and the frequency of chain breakage measured by sedimentation in either neutral or alkaline sucrose gradients. The wavelength dependence of the photochemical cross section for chain breaks paralleled that for iodine loss, and the average frequency of chain breakage per halogen loss was 0.50 ± 0.07. Approximately 80-90% of the breaks observed in alkali are alkali-labile bonds and are not observed under neutral conditions. The presence of ethanol during irradiation reduced the frequency of chain breakage by more than an order of magnitude. These results are interpreted in terms of a model in which photo-induced deiodination leads to the formation of a uracilyl radical which then abstracts a hydrogen atom from either a nearby sugar moiety or from another hydrogen donor such as ethanol. The resulting modified sugar can then rearrange to form either a clean chain break or an alkali-labile bond.     

Theoretical improvement of the specific inhibitor of human carbonic anhydrase VII

The selectivity of a known arylsulfonamides inhibitor for two isozymes II and VII of human carbonic anhydrases (hCAs) was studied by homology modeling, molecular docking and molecular dynamics methods. The results show that the selectivity of the inhibitor for two isozymes is due to the different side chain lengths between N67 of hCA II and Q64 of hCA VII. One more methene group in the side chain of Q64 of hCA VII makes it possible to form the hydrogen bond with the bromide atom of the known inhibitor. From the point of view, the modification to the known inhibitor was performed to obtain an inhibitor with higher selectivity. The complex conformations of the new designed inhibitor and two isozymes designate the formation of the hydrogen bond between the newly added group (hydroxypropyl group) and Q64 of hCA VII but N67 of hCA II. The results of the binding free energy from the MM/PBSA approach also prove the selectivity improvement of the new inhibitor in comparison with the known inhibitor. The work will help the design of the isozyme-specific inhibitors of hCA VII.     

Glycoligands tuning the magnetic anisotropy of Ni(II) complexes

Two organic ligands based on a sugar-scaffold derived from galactose and possessing three O-CH(2)-pyridine pendant arms at the 3-, 4-, and 5-positions of the galactopyranose that act as chelates afford mononuclear complexes when reacted with a Ni(II) salt. The magnetization behavior in the form of M=f(H/T) plots suggests the presence of appreciable magnetic anisotropy within the two complexes. The analysis of the EPR spectra performed at two different temperatures (7 and 17 K) and at three frequencies (190, 285, and 380 GHz) leads to the conclusion that the anisotropy has a high degree of axiality (E/D=0.17 for the two complexes), but with a different sign of the D parameter. The spin hamiltonian parameters D and E were reproduced for the two complexes by using calculations based on the angular overlap model (AOM). The structural difference between the two complexes responsible of the sign of the D parameters was also determined using AOM calculations. A thorough analysis of the structures showed that the structural differences in the coordination sphere of the two complexes responsible of the different D parameter sign result from the nature of the sugar scaffolds. In complex 1, the sugar scaffold imposes an intramolecular hydrogen bond with one of the atoms linked to Ni(II); this arrangement leads to a distorted coordination sphere and positive D value, while the absence of such a hydrogen bond in complex 2 leads to a less distorted environment around the Ni center and to a negative D value.     

紫杉醚与αβ微管蛋白的分子对接

采用Insight II/Affinity对紫杉醚与αβ微管蛋白进行分子对接, 共得到10个对接构象. 应用密度泛函B3LYP/6-31G 方法计算对接口袋构象的结合能, 筛选出结合能达-190.53 kJ·mol-1的最优对接构象5. 通过构象分析建立紫杉醚与受体结合的作用模型, 结果表明, 在活性口袋的底部紫杉醚与受体间的作用主要是疏水作用, 而在活性口袋的顶部两者间主要是氢键作用. 氢键作用位置可分为A和B两个作用区, 其中A区有3个氢键, 由C13侧链分别与受体的ASP26和ARG369作用形成; B区也有3个氢键, 是由紫杉醚母环上的极性基团分别与受体的THR276、ARG278和GLN282作用产生的. 紫杉醚与αβ微管蛋白间形成的6个氢键可以有效地将紫杉醚固定在活性口袋中.     

Synthesis of 1,2,3-triazole and 1,2,3,4-tetrazole-fused glycosides and nucleosides by an intramolecular 1,3-dipolar cycloaddition reaction

Various 1,2,3-triazole and 1,2,3,4-tetrazole fused multi-cyclic compounds were synthesized from carbohydrate derived azido-alkyne and azido-cyanide substrates. The acid sensitive 1,2-O-isopropylidene group of the furanosyl sugar was utilized for diversification to glycosides and nucleosides under Fischer glycosidation and Vorbruggen's conditions, respectively.     

The Radical Cationic Repair Pathway of Cyclobutane Pyrimidine Dimer: The Effect of Sugar‐Phosphate Backbone

Radical cationic repair process of cis–syn thymine dimer has been investigated when (1) sugar‐phosphate backbones were substituted by hydrogen atoms, (2) phosphate group was substituted by two hydrogen atoms each on a sugar ring and (3) sugar‐phosphate backbone was taken into account. The effect of the interactions between N1 and N1′ lone pairs and the C6‐C6′ antibonding orbital are the most important evidences for the cleavage of the C6‐C6′ bond in the first step of radical cationic repair mechanism in the absence of the sugar‐phosphate backbone. The impact of the N1 and N1′ lone pairs on the C6‐C6′ bond cleavage decreases and the energy barrier of the cleavage of that bond significantly increases in the presence of the deoxynucleoside sugars and the sugar‐phosphate backbone.     

Configurational statistics of polynucleotide chains. A single virtual bond treatment.

A simplified single virtual bond scheme has been developed for the calculation of mean-square unperturbed dimensions in polynucleotide chains. As a consequence of the structural rigidity of the sugar residues in the chain, it is possible to represent the six chemical bonds comprising the chain backbone repeating unit by a single virtual bond (connecting successive phosphorus atoms). The mutual orientation of a pair of adjoining virtual bonds is determined by the angles of rotation about the phosphodiester bonds adjoining intervening phosphorus atoms and is independent of the orientation of all other virtual bonds in the chain. Computed values of chain dimensions based on the single virtual bond scheme are comparable to those calculated previously using a two virtual bond model which permits rotational flexibility in the sugar moieties of the chain.     

Study of the collision-induced radical cleavage of flavonoid glycosides using negative electrospray ionization tandem quadrupole mass spectrometry

Negative electrospray ionization tandem quadrupole mass spectrometry was used to study the collision-induced dissociation (CID) of the O-glycosidic bond from different commercially available flavonoid glycosides. Depending on the structure, flavonoid glycosides can undergo both a collision-induced homolytic and heterolytic cleavage of the O-glycosidic bond producing deprotonated radical aglycone ((Y(0) - H)(-*)) and aglycone (Y(0) (-)) product ions. The relative abundance of the radical aglycone to the aglycone fragment from flavonol-3-O-glycosides increased with increasing number of hydroxyl substituents in the B ring and in the order kaempferol - 相似文献   

Hydrogen bonding on accessible surfaces of cellulose from various sources and relationship to order within crystalline regions

Celluloses from a variety of common sources were analyzed for availabilities of O(2)H, O(3)H, and O(6)H in order to estimate the extent of hydrogen bonding on accessible fibrillar surfaces. Celluloses from flax, ramie, sisal, and wood (both cellulose I and II from wood) together with liquid NH₃-swollen cotton and NaOH-swollen cotton (cellulose II) had relative availabilities similar to those of native cotton. Celluloses from Valonia centricosa and in rayon samples stood apart from each other and from the “cotton family.” The difference between Valonia and cotton celluloses appears to result, in addition to the accepted smaller, less perfect crystallites in cotton, from an O(2)H hydrogen bond which is likely the intramolecular bond between O(2)H and O(6′)H that is present in Valonia and absent in cotton. Rayon samples also showed evidence of similar bonds involving O(2)H on accessible surfaces. Since the regenerated rayons had relative availabilities different from those of mercerized cotton and wood cellulose samples, it is proposed that chain packing arrangements are not the same in these two types of cellulose II.     

Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases

Unsaturated glucuronyl hydrolases (UGLs) from GH family 88 of the CAZy classification system cleave a terminal unsaturated sugar from the oligosaccharide products released by extracellular bacterial polysaccharide lyases. This pathway, which is involved in extracellular bacterial infection, has no equivalent in mammals. A novel mechanism for UGL has previously been proposed in which the enzyme catalyzes hydration of a vinyl ether group in the substrate, with subsequent rearrangements resulting in glycosidic bond cleavage. However, clear evidence for this mechanism has been lacking. In this study, analysis of the products of UGL-catalyzed reactions in water, deuterium oxide, and dilute methanol in water, in conjunction with the demonstration that UGL rapidly cleaves thioglycosides and glycosides of inverted anomeric configuration (substrates that are resistant to hydrolysis by classical glycosidases), provides strong support for this new mechanism. A hydration-initiated process is further supported by the observed UGL-catalyzed hydration of a C-glycoside substrate analogue. Finally, the observation of a small β-secondary kinetic isotope effect suggests a transition state with oxocarbenium ion character, in which the hydrogen at carbon 4 adopts an axial geometry. Taken together, these observations validate the novel vinyl ether hydration mechanism and are inconsistent with either inverting or retaining direct hydrolase mechanisms at carbon 1.     

Supramolecular assemblies and molecular recognition of amphiphilic schiff bases with barbituric acid in organized molecular films

A bolaform Schiff base, N,N'-bis(salicylidene)-1,10-decanediamine (BSC10), has been synthesized and its interfacial hydrogen bond formation or molecular recognition with barbituric acid was investigated in comparison with that of a single chain Schiff base, 2-hydroxybenzaldehyde-octadecylamine (HBOA). It has been found that while HBOA formed a monolayer at the air/water interface, the bolaform Schiff base formed a multilayer film with ordered layer structure on water surface. When the Schiff bases were spread on the subphase containing barbituric acid, both of the Schiff bases could form hydrogen bonds with barbituric acid in situ in the spreading films. As a result, an increase of the molecular areas in the isotherms was observed. The in situ H-bonded films could be transferred onto solid substrates, and the transferred multilayer films were characterized by various methods such as UV-vis and FT-IR spectrosopies. Spectral changes were observed for the films deposited from the barbituric acid subphase, which supported the hydrogen bond formation between the Schiff bases and barbituric acid. By measuring the MS-TOF of the deposited films dissolved in CHCl3 solution, it was concluded that a 2:1 complex of HBOA with barbituric acid and a 1:2 complex of BSC10 with barbituric acid were formed. On the other hand, when the multilayer films of both Schiff bases were immersed in an aqueous solution of barbituric acid, a similar molecular recognition through the hydrogen bond occurred. A clear conformational change of the alkyl spacer in the bolaform Schiff base was observed during the complex formation with the barbituric acid.     

Force‐field parameters of the Ψ and Φ around glycosidic bonds to oxygen and sulfur atoms

The Ψ and Φ torsion angles around glycosidic bonds in a glycoside chain are the most important determinants of the conformation of a glycoside chain. We determined force‐field parameters for Ψ and Φ torsion angles around a glycosidic bond bridged by a sulfur atom, as well as a bond bridged by an oxygen atom as a preparation for the next study, i.e., molecular dynamics free energy calculations for protein‐sugar and protein‐inhibitor complexes. First, we extracted the Ψ or Φ torsion energy component from a quantum mechanics (QM) total energy by subtracting all the molecular mechanics (MM) force‐field components except for the Ψ or Φ torsion angle. The Ψ and Φ energy components extracted (hereafter called “the remaining energy components”) were calculated for simple sugar models and plotted as functions of the Ψ and Φ angles. The remaining energy component curves of Ψ and Φ were well represented by the torsion force‐field functions consisting of four and three cosine functions, respectively. To confirm the reliability of the force‐field parameters and to confirm its compatibility with other force‐fields, we calculated adiabatic potential curves as functions of Ψ and Φ for the model glycosides by adopting the Ψ and Φ force‐field parameters obtained and by energetically optimizing other degrees of freedom. The MM potential energy curves obtained for Ψ and Φ well represented the QM adiabatic curves and also these curves' differences with regard to the glycosidic oxygen and sulfur atoms. Our Ψ and Φ force‐fields of glycosidic oxygen gave MM potential energy curves that more closely represented the respective QM curves than did those of the recently developed GLYCAM force‐field. © 2009 Wiley Periodicals, Inc., J Comput Chem, 2009     

Molecular mechanics study on conformation of perylene-quinonoid photosensitizers

Using molecular mechanics method,values of the heat of formation (HF) of different conformations,of perylenequinonoid photosensitizes hypocrellin A (HA) and hypocrellin B (HB) were calculated and the variance of HF after phenolic protons' dissociation were calculated as well The following was found:(i) The HF values of lour conformational isomers of HA and HB are similar to each other,so the four isomcrs can transform to each other room temperature,(ii) There exists the difference between the ability of dissociation of phenolic protons of HA and that of HB,the former is higher than the latter (iii) There exist two intramolecular hydrogen bonds in HA and HB The bond energy is approximately 8 kJ/mol and the energy of conformation Ⅰ is lower than that of conformationⅡ The bond energy of HA is lower than that of HB.(iv) There exists a low energy snot when phenolic hydroxyl bond twists 180° from the position where hydrogen bond is formed,which suggests that this kind of conformation probably exists,(v) Th     

Three New Steroidal Glycosides from the Roots of Cynanchum auriculatum

Three new C₂₁ steroidal glycosides with a cinnamoyl group at C(12) and a 2‐methylbutanoyl group at C(20), and a straight sugar chain at C(3), namely cyanoauriculosides C–E ( 1 – 3 , resp.), together with three known steroidal derivatives, were isolated from the roots of Cynanchum auriculatum (Asclepiadaceae). Their structures were determined by spectroscopic analyses and chemical methods. The known constituents were identified as wilfoside K1N ( 4 ), cynanauriculoside II ( 5 ), and auriculoside IV ( 6 ).     

C-H activation by a mononuclear manganese(III) hydroxide complex: synthesis and characterization of a manganese-lipoxygenase mimic?

Lipoxygenases are mononuclear non-heme metalloenzymes that regio- and stereospecifically convert 1,4-pentadiene subunit-containing fatty acids into alkyl peroxides. The rate-determining step is generally accepted to be hydrogen atom abstraction from the pentadiene subunit of the substrate by an active metal(III)-hydroxide species to give a metal(II)-water species and an organic radical. All known plant and animal lipoxygenases contain iron as the active metal; recently, however, manganese was found to be the active metal in a fungal lipoxygenase. Reported here are the synthesis and characterization of a mononuclear Mn(III) complex, [Mn(III)(PY5)(OH)](CF(3)SO(3))(2) (PY5 = 2,6-bis(bis(2-pyridyl)methoxymethane)pyridine), that reacts with hydrocarbon substrates in a manner most consistent with hydrogen atom abstraction and provides chemical precedence for the proposed reaction mechanism. The neutral penta-pyridyl ligation of PY5 endows a strong Lewis acidic character to the metal center allowing the Mn(III) compound to perform this oxidation chemistry. Thermodynamic analysis of [Mn(III)(PY5)(OH)](2+) and the reduced product, [Mn(II)(PY5)(H(2)O)](2+), estimates the strength of the O-H bond in the metal-bound water in the Mn(II) complex to be 82 (+/-2) kcal mol(-)(1), slightly less than that of the O-H bond in the related reduced iron complex, [Fe(II)(PY5)(MeOH)](2+). [Mn(III)(PY5)(OH)](2+) reacts with hydrocarbon substrates at rates comparable to those of the analogous [Fe(III)(PY5)(OMe)](2+) at 323 K. The crystal structure of [Mn(III)(PY5)(OH)](2+) displays Jahn-Teller distortions that are absent in [Mn(II)(PY5)(H(2)O)](2+), notably a compression along the Mn(III)-OH axis. Consequently, a large internal structural reorganization is anticipated for hydrogen atom transfer, which may be correlated to the lessened dependence of the rate of substrate oxidation on the substrate bond dissociation energy as compared to other metal complexes. The results presented here suggest that manganese is a viable metal for lipoxygenase activity and that, with similar coordination spheres, iron and manganese can oxidize substrates through a similar mechanism.     

Palladium(II) complexes, as synthetic peptidases, regioselectively cleave the second peptide bond "upstream" from methionine and histidine side chains

Palladium(II) complexes promote hydrolysis of natural and synthetic oligopeptides with unprecedented regioselectivity; the only cleavage site is the second peptide bond upstream from a methionine or a histidine side chain, that is, the bond involving the amino group of the residue that precedes this side chain. We investigate this regioselectivity with four N-acetylated peptides as substrates: neurotransmitter methionine enkephalin (Ac-Tyr-Gly-Gly-Phe-Met) and synthetic peptides termed Met-peptide (Ac-Ala-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala), His-peptide (Ac-Val-Lys-Gly-Gly-His-Ala-Lys-Tyr-Gly-Gly-Met(OX)-Ala-Ala-Arg-Ala), in which a Met is oxidized to sulfone, and HisMet-peptide (Ac-Val-Lys-Gly-Gly-His-Ala-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala). While maintaining protein-like properties, these substrates are suitable for quantitative study since their coordination to Pd(II) ion can be determined (by NMR spectroscopy), and the cleavage fragments can be separated (by HPLC methods) and identified (by MALDI mass spectrometry). The only peptide bonds cleaved were the Gly3-Phe4 bond in methionine enkephalin, Gly4-Gly5 bond in Met-peptide, Gly3-Gly4 in His-peptide, and Gly3-Gly4 and Gly9-Gly10 bonds in HisMet-peptide. We explain this consistent regioselectivity of cleavage by studying the modes of Met-peptide coordination to the Pd(II) ion in [Pd(H(2)O)(4)](2+) complex. In acidic solution, the rapid attachment of the Pd(II) complex to the methionine side chain is followed by the interaction of the Pd(II) ion with the peptide backbone upstream from the anchor. In the hydrolytically active complex, Met-peptide is coordinated to Pd(II) ion as a bidentate ligand - via sulfur atom in the methionine side chain and the first peptide nitrogen upstream from this anchor - so that the Pd(II) complex approaches the scissile peptide bond. Because the increased acidity favors this hydrolytically active complex, the rate of cleavage guided by either histidine or methionine anchor increased as pH was lowered from 4.5 to 0.5. The unwanted additional cleavage of the first peptide bond upstream from the anchor is suppressed if pH is kept above 1.2. Four Pd(II) complexes cleave Met-peptide with the same regioselectivity but at somewhat different rates. Complexes in which Pd(II) ion carries labile ligands, such as [Pd(H(2)O)(4)](2+) and [Pd(NH(3))(4)](2+), are more reactive than those containing anionic ligands, such as [PdCl(4)](2)(-), or a bidentate ligand, such as cis-[Pd(en)(H(2)O)(2)](2+). When both methionine and histidine residues are present in the same substrate, as in HisMet-peptide, 1 molar equivalent of the Pd(II) complex distributes itself evenly at both anchors and provides partial cleavage, whereas 2 molar equivalents of the promoter completely cleave the second peptide bond upstream from each of the anchors. The results of this study bode well for growing use of palladium(II) reagents in biochemical and bioanalytical practice.     

Mechanistic studies on the formation of glycosidase-substrate and glycosidase-inhibitor covalent intermediates

Glycoside hydrolases catalyze the breaking of the glycosidic bond. This type of bond fashioned between two monosaccharides is very stable, and the polymers created are involved in multiple cellular processes, being crucial to life. In this article, computational methods were used to study the first step of the mechanism of reaction of retaining glycoside hydrolases in atomic detail. The systems modeled included a simplified reaction center and a small substrate/inhibitor. Using DFT calculations we were able to corroborate and provide molecular-level detail to the dissociative mechanism proposed in the literature. The role of the hydrogen bridge between the nucleophile and the C(2)--OH group of the ring was also investigated. Therefore, we concluded that this bridge is responsible for lowering the activation barrier by 5.1 kcal mol(-1) with functional BB1K/6-311+G(2d,2p), and the absence of the bridge explains, at least in part, the inhibitory effect of fluoro-substituted glycosides in the -2 position. The hydrogen bridge could also be involved in favoring the ring distortion verified in the transition state, and the dissociative character of the reaction mechanism. Using the NBO method, point atomic charges were calculated. In the transition state, the positive charge generated in the sugar ring is distributed nearly equally between the anomeric carbon and the ring oxygen, through a partial double bond involving the two atoms.