共查询到20条相似文献,搜索用时 15 毫秒
1.
Aggarwal R Benedetti F Berti F Buchini S Colombatti A Dinon F Galasso V Norbedo S 《Chemistry (Weinheim an der Bergstrasse, Germany)》2003,9(13):3132-3142
Amidase antibody 312d6, obtained against the sulfonamide hapten 4 a that mimics the transition state for hydrolysis of a distorted amide, accelerates the hydrolysis of the corresponding amides 1 a-3 a by a factor of 10(3) at pH 8. The mechanisms of both the uncatalyzed and antibody-catalyzed reactions were studied. Between pH 8 and 12 the uncatalyzed hydrolysis of N-toluoylindoles 1 a and 3 a shows a simple first-order dependence on [OH(-)], while hydrolysis of 3 a is zeroth-order in [OH(-)] below pH 8. The pH profile for hydrolysis of the corresponding tryptophan amide 2 a is more complex due to the dissociation of the zwitterion into an anion with pK(a) 9.74; hydrolysis of the zwitterionic and the anionic form of 2 a both show simple first-order dependence on [OH(-)]. Absence of (18)O exchange between H(2) (18)O/(18)OH(-) and the substrate, a normal SKIE for both 1 a (k(H)/k(D)=1.12) and 3 a (k(H)/k(D)=1.24) and the value of the Hammett constant rho for hydrolysis of p-substituted amides 3 a-e are consistent with an ester-like mechanism in which formation of the tetrahedral intermediate is rate-determining and the amine departs as anion. The 312d6-catalyzed hydrolysis of 3 a was studied between pH 7.5 and 9, and its independence of pH in this range indicates that water is the reacting nucleophile. Hydrolysis of 3 a is only partially inhibited by the sulfonamide hapten, and this indicates that non-specific catalysis by the protein accompanies the specific process. Only the nonspecific process is observed in the hydrolysis of amides 3 with para substituents other than methyl. Binding studies on the corresponding series of p-substituted sulfonamides 5 a-e confirm the high specificity of antibody 312d6 for p-methyl substituted substrates. 相似文献
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The Pauson-Khand reaction: the catalytic age is here! 总被引:2,自引:0,他引:2
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Marquardt A Muyldermans S Przybylski M 《Chemistry (Weinheim an der Bergstrasse, Germany)》2006,12(7):1915-1923
We describe the synthesis and characterisation of the fully functional molecular recognition structure of a 26-amino acid residue peptide antibody, referred to as peptibody, designed from a monoclonal single-domain antibody fragment derived from a camel heavy-chain antibody. The CDR3 region (CDR = complementarity determining region) of the cAbLys3 camel antibody fragment, which binds to the active site of hen eggwhite lysozyme (HEL) and acts as a potent enzyme inhibitor by mimicking an oligosaccharide substrate, was prepared by solid-phase peptide synthesis. To obtain a closed loop-like structure resembling that in the crystal structure, N- and C-terminal cysteine residues were added to the linear peptide and oxidised to a cyclic disulfide-bridged peptide by using dimethylsulfoxide. A further, internal cysteine-12 residue was acetamidomethyl-protected to prevent possible oxidative byproducts. Affinity separation on a lysozyme microcolumn combined with MALDI-TOF mass spectrometry revealed that the peptide resumed high affinity to lysozyme only after deprotection of Cys-12, suggesting the importance of this paratope sequence for epitope recognition. The complex of lysozyme and active peptibody was characterised directly by conducting high-resolution ESI-FTICR mass spectrometry, which provided a molecular comparison of affinities for linear and cyclic peptibodies. 相似文献
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K Seshadri Saraswathi Vishveshwara Mahendra K. Jain 《Journal of Chemical Sciences》1994,106(5):1177-1189
Molecular constraints for the localization of active site directed ligands (competitive inhibitors and substrates) in the
active site of phospholipase A2 (PLA2) are characterized. Structure activity relationships with known inhibitors suggest that
the head group interactions dominate the selectivity as well as a substantial part of the affinity. Theab initio fitting of the amide ligands in the active site was carried out to characterize the head group interactions. Based on a systematic
coordinate space search, formamide is docked with known experimental constraints such as coordination of the carbonyl group
to Ca2+ and hydrogen bond between amide nitrogen and ND1 of His48. An optimal position for a bound water molecule is identified and
its significance for the catalytic mechanism is postulated. Unlike the traditional “pseudo-triad” mechanism, the “Ca-coordinated-oxyanion”
mechanism proposed here invokes activation of the catalytic water to form the oxyanion in the coordination sphere of calcium.
As it attacks the carbonyl carbon of the ester, a near-tetrahedral intermediate is formed. As the second proton of the catalytic
water is abstracted by the ester oxygen, its reorientation and simultaneous cleavage form hydrogen bond with ND1 of His48.
In this mechanism of esterolysis, a catalytic role for the water co-ordinated to Ca2+ is recognised. 相似文献
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Carbon‐based solid acid catalyst has been applied to catalyzing the synthesis of 4(3H)‐quinazolinones from the cyclization reaction of 2‐aminobenzamide with aroyl chlorides. The results showed that the catalyst was very efficient with the average yield over 85%. This carbon material with strong protonic acid sites as heterogeneous catalyst has some advantages such as high activity, strikingly simple work‐up procedure, non‐pollution, and reusability, which will contribute to the green process greatly. 相似文献
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Sudhir Paul 《Applied biochemistry and biotechnology》1994,47(2-3):241-255
Catalytic antibodies may be produced over the natural course of antibody-affinity maturation by placement of chemically reactive
residues in antibody-active sites by somatic hypermutation or V-D-J-gene rearrangement. This hypothesis has received support
from recent observations on the chemical reactivity of antibodies to vasoactive intestinal peptide (VIP), DNA, and steroid-and
dinitrophenyl-esters. Recent studies reveal that monoclonal antibodies raised against the ground state of VIP can accelerate
the cleavage of peptide bonds. The light-chain (L-chain) subunit of human autoantibodies display increased hydrolytic rate
and diminished VIP-binding affinity compared to the parent antibody, consistent with increased turnover owing to weaker binding
of the substrate ground state. These observations reveal an essential limitation of catalytic antibodies, i.e., large turnover
rates may be associated with diminished substrate specificity.
The hydrolysis of VIP by IgG purified by affinity chromatography from asthma patients and nonasthmatic controls was compared.
IgG from the majority of asthma patients displayed VIP-hydrolyzing activity. Vmax values for IgG from asthmatics tended to be higher than those from the nonasthmatic group.
In principle, catalysis by antibodies may be an important mediator of immunological defense, regulation, and autoimmune dysfunction.
The verification of these possibilities will require studies that utilize efficient assays of antibody catalysis during experimental
immunization and autoimmune disease, as well as mechanistic investigation of catalysis by antibodies and their subunits. 相似文献
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V. G. Nenajdenko I. V. Golubinskii O. N. Lenkova A. V. Shastin E. S. Balenkova 《Russian Chemical Bulletin》2005,54(1):252-254
Catalytic olefination of hydrazones of aromatic aldehydes with dibromoacetonitrile affords cinnamonitriles.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 247–249, January, 2005. 相似文献
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Naoya Shindoh Yoshiji Takemoto Prof. Kiyosei Takasu Prof. 《Chemistry (Weinheim an der Bergstrasse, Germany)》2009,15(45):12168-12179
Domino reactions have received great attention as efficient synthetic methodologies for the construction of structurally complex molecules from simple materials in a single operation. Catalysts in domino reactions have also been well studied. In these reactions, a catalyst activates the substrate(s) only once, and the structure of the product is delineated at that time. Recently, the new concept of “tandem catalysis” in domino reactions, in which catalyst(s) sequentially activate more than two mechanistically distinct reactions, has been proposed. Tandem catalysis is categorized into three subclasses: orthogonal‐, auto‐, and assisted‐tandem catalyses. Auto‐tandem catalysis is defined as a process in which one catalyst promotes more than two fundamentally different reactions in a single reactor. An overview of recent and significant achievements in auto‐tandem catalysis is presented in this paper. 相似文献
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Jing‐Yi JIN Shou‐Feng WANG Wei XUAN Ji‐Wen SHENG Si‐Hong WANG Guan‐Rong TIAN 《中国化学》2008,26(1):153-157
Both enantiomers of 2‐benzyl‐5‐bromo‐4‐oxopentanoic acid were prepared utilizing the diazo ketones as the key intermediates. The compounds were assayed for inhibitory activity against carboxypeptidase A (CPA, EC 3.4.17.1). The (R)‐form is 260‐fold more potent than the corresponding (S)‐form. The finding that (R)‐form, which belongs to the L‐series, is mostly responsible for the inhibitory activity accords with the substrate specificity of CPA. For comparison, both the optical forms of 2‐benzyl‐4‐oxopentanoic acid were also synthesized and evaluated as the inhibitors against CPA. These results reveal that the introduction of a bromo group at the α‐position of ketones can significantly enhance the electrophilicity of the carbonyl group. Further molecular docking study suggested that the gem‐diol form of the α‐bromo ketone, which mimics the transition state in the CPA catalytic process, could chelate the zinc ion in the active site of CPA and thus result in the strong inhibition. 相似文献
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污泥热解中HCN与CaO的反应机理:密度泛函理论研究 总被引:2,自引:0,他引:2
污泥热解中HCN与CaO的反应机理:密度泛函理论研究 《燃料化学学报》2017,45(1):123-128
采用密度泛函理论对污泥热解中CaO与HCN在低温段的反应进行了研究。在B3LYP/6-311++(3df,2p)水平上计算得到了反应路径上各驻点的几何构型与频率,并在此构型上使用CCSD(T)/cc-pVQZ进行单点能计算。结果表明,两个HCN分子吸附于CaO后,质子发生转移时出现反应路径中最大能垒(310.33 kJ/mol)。使用经典过渡态理论拟合了反应中各步骤的阿累尼乌斯公式,计算了三种典型温度下各步骤的反应速率,发现质子转移为该反应的决速步骤,且温度越高CaO对HCN的作用效果越好。 相似文献
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Eugenia Dzib José Luis Cabellos Filiberto Ortíz-Chi Sudip Pan Annia Galano Gabriel Merino 《International journal of quantum chemistry》2019,119(2):e25686
Eyringpy is a modular program for calculating thermochemical properties and rate constants for reactions in the gas phase and in solution. The code is written in Python and it has a user-friendly interface and a simple input format. Unimolecular and bimolecular reactions with one and two products are supported. Thermochemical properties are estimated through canonical ensemble and rate constants are computed according to the transition state theory. One-dimensional Wigner and Eckart tunneling corrections are also available. Rate constants of bimolecular reactions involving the formation of pre-reactive complexes are also estimated. To compute rate constants in solution, Eyringpy uses the Collins–Kimball theory to include the diffusion-limit, the Marcus theory for electron transfer processes, and the molar fractions to account for the solvent pH effect. 相似文献
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Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids
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Kang Du Pan Guo Yuan Chen Zhen Cao Dr. Zheng Wang Prof. Dr. Wenjun Tang 《Angewandte Chemie (International ed. in English)》2015,54(10):3033-3037
A novel enantioselective palladium‐catalyzed dearomative cyclization has been developed for the efficient construction of a series of chiral phenanthrenone derivatives bearing an all‐carbon quaternary center. The effectiveness of this method in the synthesis of terpenes and steroids was demonstrated by a highly efficient synthesis of a kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and the enantioselective total synthesis of the antimicrobial diterpene natural product (?)‐totaradiol. 相似文献
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采用密度泛函理论计算方法模拟了简单钴卟啉过氧中间体PCo-O2与环己烷C6H12的作用,分析了反应路径中各驻点能量和反应过渡态分子构型。研究结果表明,PCo-O2向底物环己烷夺氢的反应可以延正方向进行,二线态PCo-O2更具反应活性,反应过程中Co-O键得到加强,O-O键被削弱。依据理论计算结果,探讨了四苯基钴卟啉催化环己烷氧化生成环己醇和环己酮的反应机理,指出反应延Lyons高价金属氧代物机理生成环己醇,而反应循环中产生的烷基自由基可以延烷基过氧化过渡金属配合物反应机理进行生成环己酮。 相似文献
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An efficient enzyme model exhibiting enantioselective esterase activity was prepared by using molecular imprinting techniques. The enantiomerically pure phosphonic monoesters 4 L and 5 L were synthesized as stable transition-state analogues. They were used as templates connected by stoichiometric noncovalent interactions to two equivalents of the amidinium binding site monomer 1. After polymerization and removal of the template, the polymers were efficient catalysts for the hydrolysis of certain nonactivated amino acid phenylesters (2 L, 2 D, 3 L, 3 D) depending on the template used. Imprinted catalyst IP4 (imprinted with 4 L) enhanced the hydrolysis of the corresponding substrate 2 L by a factor of 325 relative to that of a buffered solution. Relative to a control polymer containing the same functionalities, prepared without template 4 L, the enhancement was still about 80-fold, showing the highest imprinting effect up to now. In cross-selectivity experiments a strong substrate selectivity of higher than three was found despite small differences in the structure of the substrate and template. Plots of initial velocities of the hydrolysis versus substrate concentration showed typical Michaelis-Menten kinetics with saturation behavior. From these curves, the Michaelis constant K(M) and the catalytic constant k(cat) can be calculated. The enantioselectivity shown in these values is most interesting. The ratio of the catalytic efficiency k(cat)/K(M), between the hydrolysis of 2 L- and 2 D-substrate with IP4, is 1.65. This enantioselectivity derives from both selective binding of the substrate (K(M)L/K(M)D=0.82), and from selective formation of the transition state (k(cat)L/k(cat)D=1.36). Thus, these catalysts give good catalysis as well as high imprinting and substrate selectivity. Strong competitive inhibition is caused by the template used in imprinting. This behavior is also quite similar to the behavior of natural enzymes, for which these catalysts are good models. 相似文献
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A density functional theory study on the catalytic mechanism of hydroxycinnamoyl‐CoA hydratase‐lyase
Guangcai Ma Yulin Li Lixin Wei Yongjun Liu Chengbu Liu 《International journal of quantum chemistry》2014,114(4):249-254
Hydroxycinnamoyl‐CoA hydratase‐lyase (HCHL), a particular member of the crotonase superfamily, catalyzes the bioconversion of feruloyl‐CoA to the important flavor and fragrance compound vanillin. In this article, the catalytic mechanism of HCHL has been studied by using hybrid density functional theory method with simplified models. The calculated results reveal that the mechanism involves the hydration of the C?C double bond of feruloyl‐CoA and thence the cleavage of C? C single bond of β‐hydroxythioester. The hydration step is a typical concerted process, whereas C? C bond cleavage follows a concerted but asynchronous mechanism. The calculated energy barrier of hydration reaction is only slightly lower than that of cleavage process, implying both of two processes are rate limiting. By using three substrate analogs, the substrate specificity of HCHL was further examined. It is found that the p‐hydroxyl group of aromatic ring is necessary for the catalytic reaction. © 2013 Wiley Periodicals, Inc. 相似文献