Pyteomics—a Python Framework for Exploratory Data Analysis and Rapid Software Prototyping in Proteomics

Pyteomics is a cross-platform, open-source Python library providing a rich set of tools for MS-based proteomics. It provides modules for reading LC-MS/MS data, search engine output, protein sequence databases, theoretical prediction of retention times, electrochemical properties of polypeptides, mass and m/z calculations, and sequence parsing. Pyteomics is available under Apache license; release versions are available at the Python Package Index http://pypi.python.org/pyteomics, the source code repository at http://hg.theorchromo.ru/pyteomics, documentation at http://packages.python.org/pyteomics. Pyteomics.biolccc documentation is available at http://packages.python.org/pyteomics.biolccc/. Questions on installation and usage can be addressed to pyteomics mailing list: pyteomics@googlegroups.com      

Generating Encoded Compound Libraries for Fabricating Microarrays as a High-Throughput Protein Ligand Discovery Platform

We demonstrate an effective method for generating libraries of encoded compounds for fabricating large compound microarrays on solid supports. This method is based on one-bead, one-compound synthesis and employs a novel trilayer bead-partition scheme that ensures sufficient quantity of synthesized compounds releasable from each bead for compound microarray fabrication in high-throughput protein–ligand discovery assays.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Metal-Free,One-Pot,Rapid Synthesis of Tetrahydropyridines Using Acetic Acid as Solvent and Catalyst at Room Temperature

Acetic acid–promoted, one-pot synthesis of tetrahydropyridines has been developed under metal-catalyst-free conditions via a tandem reaction. High atom economy, good yield, simple procedure, no expensive column chromatography, shorter reaction time, and metal-free and mild reaction conditions are some of the important features of this protocol. The current methodology provides an alternative approach for not only highly substituted tetrahydropyridines (THPs) but also fully substituted tetrahydropyridines (FTHPs) in moderate to good yields. The plausible mechanism for the formation of THPs was greatly promoted by the H⁺ ion coming from acetic acid.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Silica-Functionalized CuI: An Efficient and Selective Catalyst for N-Benzylation,Allylation, and Alkylation of Primary and Secondary Amines in Water

Silica-functionalized CuI has been reported as an efficient and selective catalyst for the selective mono-N- and N,N-dibenzylation, allylation, and alkylation of primary amines with benzylic, allylic, and alkyl halides using NaOH as base in aqueous medium. By changing the reaction temperature, mono- or di-benzylation, allylation, or alkylation could be achieved in good yield and selectivity. Secondary amines have also been benzylated, allylated, and alkylated under similar conditions. SiO₂-CuI has been characterized by Fourier transform–infrared, atomic absorption spectrometry, thermalgravimetric analysis, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy, and found to be highly selective and recyclable under the reaction conditions.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Oxidative Nuclear Bromination of Substituted 4-Pyridones Using Pyridinium Bromochromate

An alternative convenient approach for the bromination of various poly-substituted 4-pyridones has been developed via an oxidative nuclear bromination in the presence of sole pyridinium bromochromate (PBC). The PBC performs the dual role of oxidant and source of Br⁺ during the process.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Total Synthesis of (±)-Glabridin

An efficient formal synthesis of (±)-glabridin was accomplished in 10 steps from resorcinol using Raney Ni to reduce carbon–carbon double bonds in α,β-unsaturated carbonyl compound as the key step.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Comparative study of GQ and QG indices as potentially favorable molecular descriptors

In chemical graph theory, several degree-based topological indices are introduced and put forward in the development of quantitative structure-property relationships (QSPR)/quantitative structure-activity relationships (QSAR) studies. However, only a few of them are considered employable in the prediction of physical and chemical properties and biological activities of molecular compounds. Here, we focus our attention on some foremost characteristics of newly defined Geometric–Quadratic $$ and Quadratic–Geometric $$ indices such as prediction power, degeneracy and structure sensitivity. Based on these attributes, we discuss their comparison with other well-established degree-based topological indices with the help of statistical analysis and computational techniques on the data sets of octane, nonane and decane isomers. Some of the graphical approaches, statistical outcomes and computational tests exhibit the dominating nature of the $$ and $$ indices over other topological indices.     

Efficient One-Pot Synthesis of 3-Amino-7-azaindoles Under Microwave Irradiation

An efficient one-pot synthesis of 3-amino-7-azaindoles was developed, starting from ethyl (3-cyanopyridin-2-yl)carbamate and α -bromoketones by microwave-assisted Thorpe–Ziegler cyclization in the presence of a base. This method features excellent yields, short reaction time (10min), and high functional group compatibility.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Efficient Method for the Synthesis of α,α′-Bis(arylmethylidene) Cycloalkanones Catalyzed by Bromodimethylsulfonium Bromide

Bromodimethylsulfonium bromide (BDMS)–catalyzed crossed aldol condensation between aromatic aldehydes and ketones is reported to access α,α′-bis(arylmethylidene) cycloalkanones at room temperature in good yields within 3–10 min. The salient features of this method are the simplicity of the procedure, the ready accessibility of the catalyst, and greater yields in relatively short reaction times.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

An Expedient Approach for the Synthesis of 1-Alkyl-4-propionylpyrrolidin-2-ones

A simple and useful tandem addition–cyclization reaction of primary amines on a prepared α-functionalized propylvinyl ketone 3 in methanol at reflux is a promising route for the synthesis of a new family of 1-alkyl-4-propionylpyrrolidin-2-ones 4.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

GalaxyDock BP2 score: a hybrid scoring function for accurate protein–ligand docking

Protein–ligand docking is a useful tool for providing atomic-level understanding of protein functions in nature and design principles for artificial ligands or proteins with desired properties. The ability to identify the true binding pose of a ligand to a target protein among numerous possible candidate poses is an essential requirement for successful protein–ligand docking. Many previously developed docking scoring functions were trained to reproduce experimental binding affinities and were also used for scoring binding poses. However, in this study, we developed a new docking scoring function, called GalaxyDock BP2 Score, by directly training the scoring power of binding poses. This function is a hybrid of physics-based, empirical, and knowledge-based score terms that are balanced to strengthen the advantages of each component. The performance of the new scoring function exhibits significant improvement over existing scoring functions in decoy pose discrimination tests. In addition, when the score is used with the GalaxyDock2 protein–ligand docking program, it outperformed other state-of-the-art docking programs in docking tests on the Astex diverse set, the Cross2009 benchmark set, and the Astex non-native set. GalaxyDock BP2 Score and GalaxyDock2 with this score are freely available at http://galaxy.seoklab.org/softwares/galaxydock.html.     

Efficient Synthesis of Some New 2,3-Dimethylquinoxaline-1-oxides Using Bis(acetoxy)phenyl-λ 3-iodane as an Oxidant

A series of 2-(arylimino)-3-(hydroxyimino)butanes 3a–g, easily accessed by the condensation of variously substituted anilines 1a–g with biacetyl monoxime 2, were efficiently cyclized to afford 2,3-dimethylquinoxaline-1-oxides 4a–g using bis(acetoxy)phenyl-λ ³-iodane as an oxidant. This methodology utilizes a commercially available and environmental benign oxidant to achieve the title compounds in excellent yields under mild conditions.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Lanthanum Triflate–Catalyzed Rapid Oxidation of Secondary Alcohols Using Hydrogen Peroxide Urea Adduct (UHP) in Ionic Liquid

A convenient and efficient protocol for the oxidation of secondary hydroxyl group to ketone using hydrogen peroxide–urea adduct and catalytic (CF₃SO₃)₃La in ionic liquid has been developed. A number of 1,2-diols, α-hydroxyketones, and other aromatic and aliphatic secondary alcohols have been successfully oxidized to the corresponding ketones using this protocol in good yields and short reaction times.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Highly Efficient Method for Synthesis of Benzoquinones Using Hypervalent Iodine(III) Reagent and Sodium Bisulfate

A rapid, one-step, novel approach for the conversion of benzamides into benzoquinones using (diacetoxyiodo)benzene(III) and sodium bisulfate has been developed in aqueous acetonitrile at room temperature. The developed protocol is applicable to several types of substituted benzamide derivatives to get the corresponding benzoquinone products. The developed methodology offers mild reaction condition, short reaction time, and moderate to excellent yields. This is one of the most simple and environmentally benign protocols for synthesis of benzamide derivatives.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

PCC-Promoted Dehydration of Aldoximes: A Convenient Access to Aromatic,Heteroaromatic, and Aliphatic Nitriles

A simple and convenient procedure for the synthesis of nitriles by dehydration of aldoximes using a PCC (pyridiniumchlorochromate) has been developed. A variety of aromatic, heteroaromatic, and aliphatic aldoximes are converted.

Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the full spectral details.     

Selective and Efficient Oxidation of Benzylic Alcohols to Benzaldehydes and Methyl Benzoates by Dibromo-5,5-dimethylhydantoin

A selective and efficient method of oxidizing benzyl alcohols to benzaldehydes and methyl benzoates by using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as oxidant is developed. One-step conversion of benzyl alcohols to methyl benzoates in methanol at room temperature for 12 hours is achieved without any catalysts. Moreover, para-substituted benzyl alcohols are obtained in 86–98% yield. When dichloromethane is used as solvent, further oxidation of benzaldehydes to esters is well controlled, selectively affording benzaldehydes in 89–99% yield within 30 minutes.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

α-二亚胺镍(Ⅱ)催化甲基丙烯酸甲酯聚合

以4种不同结构的α-二亚胺镍(Ⅱ)催化剂[(t-Bu)—N CH—CH N—(t-Bu)]NiBr₂(C1), [C₆H₅—N C(Me)—C(Me) N—C₆H₅]NiBr₂(C2), [(2,6-C₆H₃(Me)₂)—N C(Me)—C·(Me) N—(2,6-C₆H₃(Me)₂)]NiBr₂(C3)和[(2,6-C₆H₃(i-Pr)₂)—N C(An)—C(An) N—(2,6-C₆H₃(i-Pr)₂)]NiBr₂(An=acenaphthyl)(C4), 在甲基铝氧烷(MAO)作用下, 对甲基丙烯酸甲酯(MMA)进行催化聚合. 以C2为模型催化剂系统研究了Al/Ni摩尔比、 单体浓度、 聚合温度、 聚合时间和反应溶剂对催化活性及聚合物分子量的影响. 在较适合的聚合条件(催化剂用量为1.6 μmol, Al/Ni摩尔比为800, MMA浓度为2.9 mol/L, 甲苯为溶剂, 聚合温度为 60 ℃, 聚合时间为4 h)下, 讨论了催化剂结构对催化活性和聚合物分子量的影响. 研究发现, 催化剂C1~C3催化MMA聚合均得到富含间规结构的聚甲基丙烯酸甲酯(PMMA). 催化剂结构中空间位阻增大导致催化活性降低, 空间位阻最小的 C1催化活性最高[达107.8 kg/(mol Ni·h)]; 而空间位阻最大的C4催化活性仅为7.8 kg/(mol Ni·h). 催化剂结构中给电子效应增加有利于催化活性及聚合物分子量的增加. C2催化活性为62.5 kg/(mol Ni·h), 所得聚合物的分子量为5.0×10⁴; 而具有较强给电子效应的C3催化活性达到96.9 kg/(mol Ni·h), 并得到更高分子量的聚合物(7.6×10⁴).     

Facile and Efficient One-Pot Procedure for Thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines Preparation

Base-catalyzed cycloaddition reactions of heterocyclic azides with activated nitriles were studied. Convenient, efficient, and high-yield synthetic method for thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines preparation from available starting reagents without complicated protocols was elaborated. Such an approach allows creation of broad combinatorial libraries for drug discovery.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Protein–small molecule docking with receptor flexibility in iMOLSDOCK

We have earlier reported the iMOLSDOCK technique to perform ‘induced-fit’ peptide–protein docking. iMOLSDOCK uses the mutually orthogonal Latin squares (MOLSs) technique to sample the conformation and the docking pose of the small molecule ligand and also the flexible residues of the receptor protein, and arrive at the optimum pose and conformation. In this paper we report the extension carried out in iMOLSDOCK to dock nonpeptide small molecule ligands to receptor proteins. We have benchmarked and validated iMOLSDOCK with a dataset of 34 protein–ligand complexes as well as with Astex Diverse dataset, with nonpeptide small molecules as ligands. We have also compared iMOLSDOCK with other flexible receptor docking tools GOLD v5.2.1 and AutoDock Vina. The results obtained show that the method works better than these two algorithms, though it consumes more computer time. The source code and binary of MOLS 2.0 (under a GNU Lesser General Public License) are freely available for download at https://sourceforge.net/projects/mols2-0/files/.