Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Library Automation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2000

Parallel synthesis of a library of 1,4-naphthoquinones and automated screening of potential inhibitors of trypanothione reductase from Trypanosoma cruzi.

Solid- and solution-phase parallel syntheses of 1,4-naphthoquinones (1,4-NQ) are described. A library of 1360 amides was constructed from the combination of 12 newly synthesised 1,4-NQ carboxylic acid and 120 amines, and was screened for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi. The most active hits from a primary screening were re-synthesised and confirmed. This approach proves that it is possible to design potent and highly specific TcTR inhibitors deriving from menadione, juglone and plumbagin.

Animals↗
PubMed2000

Titanium(IV) isopropoxide mediated solution phase reductive amination on an automated platform: application in the generation of urea and amide libraries.

Amine libraries and their derivatives are important targets for high throughput synthesis because of their versatility as medicinal agents and agrochemicals. As a part of our efforts towards automated chemical library synthesis, a titanium(IV) isopropoxide mediated solution phase reductive amination protocol was successfully translated to automation on the Trident(TM) library synthesizer of Argonaut Technologies. An array of 24 secondary amines was prepared in high yield and purity from 4 primary amines and 6 carbonyl compounds. These secondary amines were further utilized in a split synthesis to generate libraries of ureas, amides and sulfonamides in solution phase on the Trident(TM). The automated runs included 192 reactions to synthesize 96 ureas in duplicate and 96 reactions to synthesize 48 amides and 48 sulfonamides. A number of polymer-assisted solution phase protocols were employed for parallel work-up and purification of the products in each step.

Amides↗
PubMed2006

Diversity-oriented synthesis of pochonins and biological evaluation against a panel of kinases.

Pochonins A-F were recently characterized as six new members of the naturally occurring family of 14-membered resorcylic acid lactones. As there are a high number of ATPase and kinase inhibitors among natural resorcylic lactones, a library based on the pochonin scaffold, with five points of diversity, was prepared which includes diversity beyond that of the natural analogues. The library was synthesized by using solid-supported reagents amenable to automation. Testing the library for its inhibition against a panel of 24 kinases at 10 microM afforded a >14 % hit rate. These results demonstrate the potential of the resorcylides towards the inhibition of therapeutically relevant kinases.

Adenosine Triphosphatases↗
PubMed2003

Evaluation of an improved general unknown screening procedure using liquid chromatography-electrospray-mass spectrometry by comparison with gas chromatography and high-performance liquid-chromatography--diode array detection.

This paper presents an improved, comprehensive liquid chromatography-electrospray-mass spectrometry (LC-ES-MS) general unknown screening (GUS) procedure for drugs and toxic compounds and its comparison with conventional techniques in routine laboratory conditions. Chromatographic separation involved an X-TERRA MS C18, 3.5 microm (100 mm x 1 mm i.d.) column together with a 25-min long gradient of acetonitrile in pH 3, 2 mM ammonium formate delivered at a 50 microl/min flow rate. Two different in-source collision-induced dissociation voltages were alternated, both in the positive and in the negative ion modes. Reconstructed spectra were then obtained in both polarities by adding up spectra obtained with low and high energy, resulting in spectra presenting a sufficient number of specific fragment ions for unambiguous and fast identification of compounds. Two large mass spectral libraries of drugs and toxic compounds were built and an efficient automated signal processing, library searching and report editing algorithm developed. Using a common, efficient solid-phase extraction procedure, this LC-ES-MS technique was compared to GC-MS and HPLC-DAD GUS procedures for the identification of a priori unknown compounds in 51 serum samples consecutively sent to the laboratory for GUS. The present LC-MS method identified 75% of the compounds contained in these samples (versus 66% for GC-MS and 71% for HPLC-DAD), including 8% that the other two techniques failed to identify (versus 8% for GC-MS and 9.5% for HPLC-DAD). Therefore, it is complementary to GC-MS and/or HPLC-DAD and helps enlarge the range of drugs detected in clinical toxicology. It could be useful as well in forensic toxicology to confirm a positive result, as 38% of all the compounds were detected by the three techniques and 36% by two of them.

Blood Chemical Analysis↗
PubMed1999

Method for determining protein kinase substrate specificities by the phosphorylation of peptide libraries on beads, phosphate-specific staining, automated sorting, and sequencing.

A method is described for the elucidation of the peptide substrate phosphorylation specificity of a protein kinase. Peptide libraries with two to six degenerate positions and a length of seven or nine amino acids were generated directly on Sepharose beads by solid-phase peptide synthesis according to the split-and-mix procedure. The immobilized peptides were incubated with the catalytic subunit of the cyclic AMP-dependent protein kinase (PKA) as a model enzyme resulting in the phosphorylation of the beads that contain the recognition motif of the kinase. The beads were then stained with a new phosphate-monoester-specific fluorescent dye consisting of a complex of iron(III) with fluorescein-coupled iminodiacetic acid. A flow cytometer was used to analyze the phosphorylation efficiency and the beads with the highest phosphorylation degree were isolated by the use of a fluorescence-activated cell sorter. Pool sequencing of those beads revealed the preferred kinase motif. The results are in good agreement with data from the literature. The method lends itself to the rapid elucidation of the specificity of uncharacterized protein kinases.

Amino Acid Sequence↗
PubMed1994

SAIL: automating interlibrary loan.

The National Library of Medicine (NLM) initiated the System for Automated Interlibrary Loan (SAIL) pilot project to study the feasibility of using imaging technology linked to the DOCLINE system to deliver copies of journal articles. During the project, NLM converted a small number of print journal issues to electronic form, linking the captured articles to the MEDLINE citation unique identifier. DOCLINE requests for these journals that could not be filled by network libraries were routed to SAIL. Nearly 23,000 articles from sixty-four journals recently selected for indexing in Index Medicus were scanned to convert them to electronic images. During fiscal year 1992, 4,586 scanned articles were used to fill 10,444 interlibrary loan (ILL) requests, and more than half of these were used only once. Eighty percent of all the articles were not requested at all. The total cost per article delivered was $10.76, substantially more than it costs to process a photocopy request. Because conversion costs were the major component of the total SAIL cost, and most of the articles captured for the project were not requested, this model was not cost-effective. Data on SAIL journal article use was compared with all ILL requests filled by NLM for the same period. Eighty-eight percent of all articles requested from NLM were requested only once. The results of the SAIL project demonstrated that converting journal articles to electronic images and storing them in anticipation of repeated requests would not meet NLM's objective to improve interlibrary loan.

Automation↗
PubMed2006

Toward automated biochemotype annotation for large compound libraries.

Combinatorial chemistry allows scientists to probe large synthetically accessible chemical space. However, identifying the sub-space which is selectively associated with an interested biological target, is crucial to drug discovery and life sciences. This paper describes a process to automatically annotate biochemotypes of compounds in a library and thus to identify bioactivity related chemotypes (biochemotypes) from a large library of compounds. The process consists of two steps: (1) predicting all possible bioactivities for each compound in a library, and (2) deriving possible biochemotypes based on predictions. The Prediction of Activity Spectra for Substances program (PASS) was used in the first step. In second step, structural similarity and scaffold-hopping technologies are employed. These technologies are used to derive biochemotypes from bioactivity predictions and the corresponding annotated biochemotypes from MDL Drug Data Report (MDDR) database. About a one million (982,889) commercially available compound library (CACL) has been tested using this process. This paper demonstrates the feasibility of automatically annotating biochemotypes for large libraries of compounds. Nevertheless, some issues need to be considered in order to improve the process. First, the prediction accuracy of PASS program has no significant correlation with the number of compounds in a training set. Larger training sets do not necessarily increase the maximal error of prediction (MEP), nor do they increase the hit structural diversity. Smaller training sets do not necessarily decrease MEP, nor do they decrease the hit structural diversity. Second, the success of systematic bioactivity prediction relies on modeling, training data, and the definition of bioactivities (biochemotype ontology). Unfortunately, the biochemotype ontology was not well developed in the PASS program. Consequently, "ill-defined" bioactivities can reduce the quality of predictions. This paper suggests the ways in which the systematic bioactivities prediction program should be improved.

Chemistry, Pharmaceutical↗
PubMed2005

Serial analyses of gene expression (SAGE).

Serial analysis of gene expression (SAGE) is a molecular biology technique that was developed to measure the global gene expression levels. It has been applied successfully to characterize transcriptomes, compare the transcript levels between normal and diseased tissues, and uncover novel molecules within defined signal transduction pathways. A detailed description is presented in this chapter of the procedures involved to prepare the SAGE libraries. Protocols for automated sequencing and other standard molecular biology techniques can be found elsewhere, and thus are not included herein.

Automation↗
PubMedDate not supplied

Automated parallel solid-phase synthesis and anticancer screening of a library of peptide-tethered platinum(II) complexes.

The automated parallel solid-phase synthesis of a 36-member library of peptide-tethered platinum(II) complexes is described. The identity and quality of each product were confirmed by mass spectrometry and (1)H NMR. Subsequently, each compound was screened for in vitro anticancer activity by treating the A2780 (human ovarian carcinoma) cell line with two concentrations of the drugs (100 and 10 microM) in quadruplicate. The reduction of cell proliferation induced by the drugs at these concentrations was determined with the MTT colorimetric assay (MTT = 3-(4',5'-dimethylthiazol-2'-yl)-2,5-diphenyltetrazolium bromide) and compared to cisplatin. Even though no very active library members could be identified, five apparently most active (8[1], 8[4], 8[10], 8[13], and 8[24]) and two inactive complexes (8[33] and 8[34]) were purified using gel permeation chromatography and fully characterized by NMR spectroscopy ((1)H, (195)Pt) and MS. The IC(50) values of these complexes and cisplatin in A2780 cells were subsequently determined using the MTT assay in a conventional manner. All seven complexes have an IC(50) above 100 microM, confirming the results generated by the assay at 100 and 10 microM of the crude reaction products.

Cell Line, Tumor↗
PubMed1967

Library statistics of schools in the health sciences. II.

This report is a continuation of "Library Statistics of Health Science Libraries: Part I," published in the July 1966 issue of the Bulletin. Interlibrary loan transactions, space assigned to library functions, historical collections, pharmacy libraries, new library construction, and automation are covered in this paper. Questions are raised concerning the adaptation of a general university library questionnaire to the subset of health science libraries.

Canada↗
PubMed1993

Multiple sequence analysis: pool sequencing of synthetic and natural peptide libraries.

Sequence analysis by automated Edman degradation has been one of the most powerful tools for the characterization of peptides for many years. Its sensitivity allows experiments in the low picomole range, and its results provide complete information about the primary structure of proteins and peptides. A new method in protein and peptide sequencing has been developed which allows for the direct application of automated Edman degradation to the analysis of peptide mixtures. With the aid of multiple sequence analysis, first, sequence motifs of isolated, naturally processed peptides binding to MHC molecules have been defined. Second, the method proved to be a valuable and reliable tool for the characterization of synthetic peptide libraries, and third, the specificity of proteases has been determined in a fast and efficient way.

Amino Acid Sequence↗