A constraints generator in structural determination by microcomputer

We present a new expert system: a constraints generator for structure determination of natural products. The constraints that the system furnishes are: skeleton (reliability: 95%), large substructures (reliability: 98%) and their associated assignments (reliability: 90%) This system is intended for structure determination of carbon-rich compounds (sesqui-, di- and triterpenes, sterols etc.) for which most structures generators are not very effective. We also present a new algorithm that can avoid the combinatorial explosion during subspectrum/substructure analysis.

Ditregra - An auxiliary program for structural determination of diterpenes

This work describes the creation of heuristics rules based on 13C-NMR spectroscopy that characterize several skeletal types of diterpenes. Using a collection of 2745 spectra we built a database linked to the expert system SISTEMAT. Several programs were applied to the database in order to discover characteristic signals that identify with a good performance, a large diversity of skeletal types. The heuristic approach used was able to differentiate groups of skeletons based firstly on the number of primary, secondary, tertiary and quaternary carbons, and secondly the program searches, for each group, if there are ranges of chemical shifts that identifies specific skeletal type. The program was checked with 100 new structures recently published and was able to identify the correct skeleton in 65 of the studied cases. When the skeleton has several hundreds of compounds, for example, the labdanes, the program employs the concept of subskeletal, and does not classify in the same group labdanes with double bounds at different positions. The chemical shift ranges for each subskeletal types and the structures of all skeletal types are given. The consultation program can be obtained from the authors. © 1997 - IOS Press. All rights reserved.

NATURAL PRODUCT SUBSTITUTION PATTERN AND SKELETAL RECOGNITION METHOD

This work describes a methodology for identification of skeletal types of diterpenes based on data base with 1500 compounds isolated from Asteraceae. One program named BOTOCSYS was built with the codification of the compounds and their botanical sources. An example of identification of a new substance is given.

Turbinatine, a potential key intermediate in the biosynthesis of corynanthean-type indole alkaloids

Extraction of the leaves of Chimarrhis turbinata has led to the isolation of turbinatine (1), a new corynanthean-type indole alkaloid, besides four known indole alkaloids, strictosidine, 5alpha-carboxystrictosidine, vallesiachotamine, and isovallesiachotamine. The structural determination of 1 was based on 1D and 2D spectroscopic data. An evaluation of the DNA-damaging activities of the isolates was performed by means of a bioassay using mutant strains of Saccharomyces cerevisiae, which indicated these compounds were weakly active.

A program for terpenoid skeleton prediction based on botanical information

This paper describes a new program developed to the SISTEMAT expert system, the SISOCBOT program. This program employs the botanical data analysis and predicts, at the end of analysis, the probable skeleton of a compound based on the input of family or genus names. The SISOCBOT program was tested with 78 samples involving 302 substances, pertaining to 38 carbon skeletons, and showed a high hit index on skeleton prediction, thus emphasizing the potential importance of these data for structural determination of natural products. © 2002 Elsevier Science Ltd. All rights reserved.

The inhibition of 5-enolpyruvylshikimate-3-phosphate synthase as a model for development of novel antimicrobials

EPSP synthase (EPSPS) is an essential enzyme in the shikimate pathway, transferring the enolpyruvyl group of phosphoenolpyruvate to shikimate-3-phosphate to form 5-enolpyruvyl-3-shikimate phosphate and inorganic phosphate. This enzyme is composed of two domains, which are formed by three copies of βαβαββ-folding units; in between there are two crossover chain segments hinging the nearly topologically symmetrical domains together and allowing conformational changes necessary for substrate conversion. The reaction is ordered with shikimate-3-phosphate binding first, followed by phosphoenolpyruvate, and then by the subsequent release of phosphate and EPSP. N-[phosphomethyl]glycine (glyphosate) is the commercial inhibitor of this enzyme. Apparently, the binding of shikimate-3-phosphate is necessary for glyphosate binding, since it induces the closure of the two domains to form the active site in the interdomain cleft. However, it is somehow controversial whether binding of shikimate-3-phosphate alone is enough to induce the complete conversion to the closed state. The phosphoenolpyruvate binding site seems to be located mainly on the C-terminal domain, while the binding site of shikimate-3-phosphate is located primarily in the N-terminal domain residues. However, recent results demonstrate that the active site of the enzyme undergoes structural changes upon inhibitor binding on a scale that cannot be predicted by conventional computational methods. Studies of molecular docking based on the interaction of known EPSPS structures with (R)- phosphonate TI analogue reveal that more experimental data on the structure and dynamics of various EPSPS-ligand complexes are needed to more effectively apply structure-based drug design of this enzyme in the future. © 2007 Bentham Science Publishers Ltd.

Prospecção química e biológica do fungo endofítico Camarops sp. isolado de Alibertia macrophylla (Rubiaceae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudos estruturais experimentais e teóricos com proteínas do veneno da serpente Bothrops jararacussu

Pós-graduação em Ciências Biológicas (Genética) - IBB

Estudo químico e biológico de fungos endofídicos associados a Senna spectabilis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo químico e busca de substâncias bioativas de Garcinia brasiliensis

Pós-graduação em Química - IQ

Prospecção química e biológica do fungo endofítico Saccharicola sp. isolado de Eugenia jambolana

Pós-graduação em Química - IQ

Ab initio protein folding simulations using atomic burials as informational intermediates between sequence and structure

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Identification of quinolactin alkaloids from fungi associated to Brazilian red algae Dichotomaria marginata by LC-PDA-MS and LC-MSn

Fungi isolated from marine organisms have been shown to produce several interesting secondary metabolites with important biological activities. Such chemical diversity may be associated to environmental stress conditions and may represent an important source of NCE for bioprospection. Quinolactins belong to a rare fungi-alkaloid class with a unique N-methyl-quinolone moiety fused to a lactam ring and present several bioactivities1. Fungi strain Dm1 was isolated from red alga Dichotomaria marginata, collected from Brazil SE coast, and was grown in sterile rice solid media at 26oC 2, which was then extracted with MeOH. The MeCN fr. from the MeOH extract was chromatographed over Sephadex LH-20 and fr. 4 afforded quinolactin (QL) alkaloids B1, B2 and A, whereas fr. 5 afforded quinolactin D1 after purification by HPLC-DAD. Structural determination of pure compounds was based on HRMS, UV, and NMR spectral analyses, in addition to comparison with literature data and Antimarin® databank. UV data indicated the presence of similar chromophores with λmax at ca. 247 and 320nm. HRMS and tandem MS analyses using both negative and positive ion modes for the isolated compounds indicated their molecular formula and structural features, as for QL B1: C15H16O2N2 [M+H 257], which showed one fragment at m/z 214 [-CHNO]; QL B2: C15H16O3N2 [M+H 273], with product ions at m/z 230 [-CHNO.] and m/z 186 [-C4H9NO.]; for QL A: C16H18N2O2 [M+H 271], which presented one ion at m/z 214, due to loss of fragment (-C4H9) from the molecular ion; and for QL D1: C16H18N2O3 [M+H 287], with product ions at m/z 186 [-CHNO] and m/z 230 [-C4H9]. Such data suggested fragmentation proposals, e.g. for Quinolactin B1 (Fig. 1), which confirmed the structures of the isolated quinolactins, and may represent an important contribution for the sustainable exploration of marine biodiversity.

Structural characterization and Curie temperature determination of a sodium strontium niobate ferroelectric nanostructured powder

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determination of the numerical parameters of a continuous damage model for the structural analysis of clay brick masonry

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)