Surface recognition of a protein using designed transition metal complexes.

Each protein has a unique pattern of histidine residues on the surface. This paper describes the design, synthesis, and binding studies of transition metal complexes to target the surface histidine pattern of carbonic anhydrase (bovine erythrocyte). When the pattern of cupric ions on a complex matches the surface pattern of histidines of the protein, strong and selective binding can be achieved in aqueous buffer (pH = 7.0). The described method of protein recognition is applicable to proteins of known structures. With rapidly increasing number of solved protein structures, the method has wide applicability in purification, targeting, and sensing of proteins.     

A designed beta-hairpin peptide for molecular recognition of ATP in water

A designed 12-residue beta-hairpin peptide with a diagonal tryptophan (Trp) pair was shown to bind ATP in water through a combination of aromatic and electrostatic interactions. The affinity for ATP was 5800 M-1 (DeltaG approximately -5.0 kcal/mol), a remarkable affinity for a short, structured peptide in water, consisting of entirely natural amino acid residues. Proton NMR measurements indicate that the adenine ring of the nucleotide is intercalated between the diagonal tryptophans in the bound state. Delineation of the contributions to ATP binding to the hairpin suggest that aromatic interactions contribute approximately -1.8 kcal/mol, while individual electrostatic interactions involving the ATP phosphates and positively charged side chains of the hairpin contribute approximately -1 kcal/mol each. The designed beta-hairpin receptor presents a novel minimalist system to investigate the energetic contributions to protein-nucleic acid recognition through the surface of a beta-sheet.     

一种变压器油色谱峰识别算法的设计

在变压器油色谱峰识别领域,传统的一阶导数法需要斜率阈值来实现色谱峰识别,因此自动化程度低及容易失真。针对这些缺点,本文在一阶导数法的基础上进行了改进,将迭代移动平均及归一化分析技术应用到色谱峰识别中,通过对信号曲线及方波曲线多次迭代移动平均确定最优的归一化识峰参数,结合色谱峰的绝对保留时间及识峰窗口实现对色谱峰的准确识别。实验结果表明：该算法可以准确识别色谱峰,对噪声、色谱峰的峰宽及峰形变化不敏感,具有很强的自适应性,满足变压器油中气体在线监测装置的现场使用要求。     

A new prenylated arylbenzofuran derivative from Morus alba L.

<正>2-[3,5-Di-O-β-D-glucosyl-4-(3-methylbut-2-enyl)phenyl]benzofuran-6-ol,a new prenylated arylbenzofuran derivative was isolated from Morus alba L.Its structure was elucidated by various spectroscopic methods including MS,~1H NMR,~(13)C NMR,DEPT,~1H-~1HCOSY,HMQC and HMBC.     

A new prenylated xanthone from Garcinia xipshuanbannaensis Y.H. Li

A new prenylated xanthone, named bannaxanthone I, has been isolated from the leaves of Garcinia xipshuanbannaensis, along with five other known compounds, bannaxanthone E, mangostinone, tovophyllin A, garcinone E, and γ-mangostin. The structure of the new compound was elucidated on the basis of high-resolution fast atom bombardment mass spectra (HRFABMS), 1D-and 2D-NMR experiments, including heteronuclear multiple bond connectivity (HMBC), heteronuclear single quantum coherence (HSQC) and 1H-1H-COSY (correlated spectroscopy, COSY).     

A differential scanning calorimetric study of cysteine hydrochloride monohydrate

An irreversible phase change, ΔH (transition) = 5.44 ± 0.11 kcal mol^?1 at 337.1 ± 0.3 K has been confirmed in L-(+)-cysteine hydrochloride monohydrate. Phase transitions resulting from thermal pretreatment are also reported and discussed.     

A general highly efficient access to prenylated phenolic natural products. Synthesis of colletochlorins B and D

A general approach is reported for the synthesis of phenolic natural products having terpenoid side chains: (1) construction of the requisite bromophenol ethers, (2) coupling the aromatic ring with a terpenoid chain through copper(I) ate complex, and (3) ether cleavage under neutral or basic conditions, and the feasibility of this strategy is demonstrated by efficient synthesis of colletochlorins B and D.     

A comparative thermogravimetric study of polymers designed as dry-developing photoresists

We report a thermogravimetric study of the uncatalyzed and photo-acid-catalyzed decomposition of a series of polyformals and polycarbonates. Some of these polymers have previously been proposed as solventless photoresists. Such polymers should decompose at much lower temperatures when heated in the presence of strong acid than when heated in the absence of acid. In addition, decomposition should lead only to volatile break-down products. We found that most of these polymers underwent clean uncatalyzed thermal decomposition. When heated in the presence of acid, the onset of thermal decomposition occurred at much lower temperatures, as expected, but was accompanied by formation of significant amounts of non-volatile product. We also found that the extent of acid-catalyzed cross-linking (i.e., formation of non-volatile product) in the benzylic polyformals was greater than that for benzylic polycarbonates.     

A mechanistic and synthetic study of organocopper substitution reactions with some homoallylic and cyclopropylcarbinyl substrates : Application to isoprenoid synthesis

The double bond of cholesteryl and 5-norbornen-2-yl tosylates and the cyclopropane ring of cyclopropylmethylcarbinyl tosylate participate in organocuprate substitution reactions; retention of configuration at the nucleofugal sp³-C atom and skeletal reorganizations are observed. A plausible mechanism for these reactions is discussed. Coupling of homogeranyl iodide with a four-carbon, functionalized, vinylic cuprate reagent is applied to stereospecific synthesis of trans, trans-farnesol.     

Molecular recognition of guanosine and 2-acetylaminofluorene-modified guanosine. A comparative study

Abstract

The ability of an abiotic receptor, 7-acetylamino-2-methyl–1,8-naphthyridine, to bind to guanosine was analysed by a combination of NMR determinations and molecular modeling studies. The results indicate that this receptor simulates the base-pairing properties of cytidine in its Watson-Crick interaction with guanosine. Binding of the same receptor to N-(guanosin-8-yl)-2-acetylaminofluorene, the guanosine adduct containing the carcinogen 2-acetylaminofluorene, was found to occur in a similar manner. The calculated binding energies show that the molecular recognition of the adduct is lower than that of the unmodified guanosine. The theoretical studies suggest that the predominance of an abnormal low energy syn conformation for the adduct is the main structural feature accounting for the observed decrease of the host-guest interaction.     

Stereospecific peptide folds. A rationally designed molecular bracelet

A canonical planar beta-hairpin peptide, stereochemically reengineered into a semicircular bracelet type motif by L-to-D stereochemical inversion in two pairs of its cross-strand neighbor residues, displays protein like ordering including two-state behavior in H2O, which is unusual for a small peptide of this size.     

A DFT study on the microscopic ionization of cysteine in water

The molecular equilibria involved in the second and third macroscopic deprotonation processes of Cys have been theoretically characterized at B3LYP/6-31++G** computing level. The role of solvent was analyzed by using the supermolecule (up to six discrete water molecules), the continuum, and the hybrid supermolecule-continuum models. Also, a novel approach to reveal the solvation effect of the bulk water was employed. Calculations performed with the supermolecule or the Onsager models overestimate absolute pK_as, whereas the PCM continuum model yields data much closer to the experimental values. The supermolecule-PCM approach estimates the pK_a values for the amino group much better than for the thiol group.     

The molecular recognition of phosphorylated proteins by designed polypeptides conjugated to a small molecule that binds phosphate

The conjugation of polypeptides from a designed set to the small molecule ligand 3,5-bis[[bis(2-pyridylmethyl)amino]methyl]benzoic acid, which in the presence of Zn(2+) ions binds inorganic phosphate, has been shown to provide a polypeptide conjugate that binds α-casein, a multiply phosphorylated protein, with a dissociation constant K(D) of 17 nM. The measured affinity is more than three orders of magnitude higher than that of the small molecule ligand for phosphate and the binding of 500 nM of α-casein was not inhibited by 10 mM phosphate buffer, providing a 2000-fold excess of phosphate ion over protein. The selectivity for phosphoproteins was demonstrated by extraction of α-casein from solutions of various complexity, including milk and human serum spiked with α-casein. In addition to α-casein, β-casein was also recognized but not ovoalbumin. Conjugation of a polypeptide to the zinc chelating ligand was therefore shown to give rise to dramatically increased affinity and also increased selectivity. A set of polypeptide conjugates is expected to be able to capture a large number of phosphorylated proteins, perhaps all, and in combination with electrophoresis or mass spectrometry become a powerful tool for the monitoring of phosphorylation levels. The presented binder can easily be attached to various types of surfaces; here demonstrated for the case of polystyrene particles. The example of phosphoproteins was selected since posttranslational phosphorylation is of fundamental importance in cell biology due to its role in signaling and therefore of great interest in drug development. The reported concept for binder development is, however, quite general and high-affinity binders can conveniently be developed for a variety of proteins including those with posttranslational modifications for which small molecule recognition elements are available.     

A computational experiment to study hydrogenations of various unsaturated compounds catalyzed by a rationally designed metal-free catalyst

Metal-free hydrogenation has been proposed to be a green alternative to the conventional hydrogenation mediated by precious transition metal complexes. Thanks to the discovery of FLP (frustrated Lewis pair) chemistry, the field has recently witnessed significant progress. Inspired by the FLP idea of synergically utilizing the catalytic effects of Lewis acid and base, we previously proposed a strategy to construct metal-free active sites for H(2) activation and designed a metal-free molecule (1) that shows high reactivity toward H(2). Encouraged by the recent experimental successes in applying the strategy, we have computationally explored if 1 can go further to serve as a catalyst to promote the hydrogenations of various unsaturated compounds examined by ethylene (CH(2)=CH(2) (4)), silyl enol ether (CH(2)=C(Me)OSiMe(3) (5)), imines (Me(2)C=NMe (6) and Ph(Me)C=NMe (7)), and ketone (Ph(Me)C=O (9)). The energetic results predicted at the M05-2X(IEFPCM, solvent = THF)/6-311++G** level indicate that these reactions have feasible kinetics and thermodynamics for experimental realization. The hydride transfer step follows the concerted mechanism, although the transfer process has asynchronous character for silyl enol ether (5) and imines (6 and 7). In addition, we have investigated the binding of CO(2) to 1 and the 1-mediated hydrogenation of CO(2).     

The development of a fluorescence turn-on sensor for cysteine, glutathione and other biothiols. A kinetic study

Two fluorescence probes for the detection of cysteine (Cys), glutathione (GSH) and other biothiols, such as homocysteine (Hcy) and cysteinyl-glycine (Cys-Gly), were developed. These molecular probes are coumarin-based derivatives containing a chalcone-like moiety that reacts with biothiols through a Michael addition reaction, leading to strong fluorescence enhancements. The reactivity of the tested biothiols toward both probes (ChC1 and ChC2) follows the order Cys > GSH > Hcy > Cys-Gly, ChC1 being less reactive than ChC2. Possible interference with other amino acids was assessed. ChC1 and ChC2 display a highly selective fluorescence enhancement with thiols, allowing these probes to be used for fluorimetric thiol determination in SH-SY5Y cells.