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At least 91 records · Page 5Linked to original sources
PubMed1997

Selection of a histidine-containing inhibitor of gelatinases through deconvolution of combinatorial tetrapeptide libraries.

A fully automated peptide synthesizer was used to generate tetrapeptide sublibraries from 24 natural and nonnatural amino acids, from which new inhibitors of gelatinases (matrix metalloproteinases MMP-2 and MMP-9) were selected as potential anticancer drugs. MMP-2 and MMP-9 from mouse Balbc/3T3 fibroblasts conditioned media were assayed in their linear range response by zymography to quantify inhibition at each step of the tetrapeptide library deconvolution. The histidine-epsilon-amino caproic acid-beta-alanine-histidine (His-epsilon Ahx-beta Ala-His) sequence was found to yield optimal inhibition of both MMP-2 and MMP-9. Inhibition by selected tetrapeptides was also evaluated with two other techniques, a native type IV collagen degradation assay and a fluorogenic enzymatic assay, confirming the tetrapeptide potency. The His-epsilon Ahx-beta Ala-His tetrapeptide also inhibited purified human MMP-2 and MMP-9 and the corresponding enzymes present in conditioned media from human tumour cells. Finally, the length of the spacer between the two terminal histidines was found to be crucial to the inhibitory potential. This approach may thus be considered as a-successful strategy to yield specific peptide or pseudopeptide inhibitors, although their potency remains moderate, since it was measured before any chemical optimization was undertaken.

3T3 Cells↗
PubMed1970

The design of the automated serials accession system at the Library of the Mount Sinai School of Medicine of the City University of New York.

This paper describes the development of the Automated Serials Accession System. It demonstrates the logic used in the design of the mechanized system and how the problems encountered were handled. The areas of cooperation with the Medical Library Center of New York and the types of programs needed to run the system are explained.

Electronic Data Processing↗
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↗
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↗
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↗
PubMed1968

Metropolitan Detroit's network: "...informed by magic numbers".

Wayne State University Library's serials automation project is evolutionary in concept, with its first completed stage designed to give information on titles and holdings. Its master tape includes, in addition to Wayne State University holdings, data for more than twenty biomedical libraries in the area, and print options are available that will produce a full union list or individual lists singly or in any combination.

Catalogs, Union as Topic↗
PubMed1999

Natural Products in High Throughput Screening: Automated High-Quality Sample Preparation.

At present, compound libraries from combinatorial chemistry are the major source for high throughput screening (HTS) programs in drug discovery. On the other hand, nature has been proven to be an outstanding source for new and innovative drugs. Secondary metabolites from plants, animals, and microorganisms show a striking structural diversity that supplements chemically synthesized compounds or libraries in drug discovery programs. Unfortunately, extracts from natural sources are usually complex mixtures of compounds, often generated in time-consuming and, for the most part, manual processes. Because quality and quantity of the provided samples play a pivotal role in the success of HTS programs, this poses serious problems. In order to make samples of natural origin competitive with synthetic compound libraries, we devised a novel, automated sample preparation procedure based on solid-phase extraction (SPE). By making use of modified Zymark (Hopkinton, MA) RapidTrace® SPE workstations, we developed an easy-to-handle and effective fractionation method that generates high-quality samples from natural origin, fulfilling the requirements for an integration in high throughput drug discovery programs.

Journal Article↗
PubMed2000

Single bead and hard tag decoding using accurate isotopic difference target analysis-encoded combinatorial libraries.

A single fully automated generic microbore liquid chromatography electrospray time-of-flight protocol has been developed for the analysis of single beads, single beads with analytical constructs, and isotopically labelled dialkylamine hard tags. The protocol relies upon the incorporation of an isotopic signature into the linker and/or derivatising molecule to give a specific isotopic ratio together with an accurate isotopic difference. These properties facilitate highly specific and sensitive analysis of beads and hard tags using accurate isotopic difference analysis (AIDA) without prior knowledge of the molecular weight. Three open access methods with automated processing have been developed around a core generic approach.

Amines↗
PubMed1998

Two-hybrid systematic screening of the yeast proteome.

The yeast two-hybrid system is a genetic method that detects protein-protein interactions. One application is the detection by library screening of new interactors of a protein of known function. In the August issue of Nature Genetics, Fromont-Racine et al. showed for the first time that the construction of the protein interaction map of a complex pathway, such as that of the mRNA splicing machinery, is now possible, because of the combination of recent technical improvements elaborated in several laboratories. With a yeast cell mating procedure that increases screen efficiency, they used their complex yeast genomic library of 5 x 10(6) clones to test 700 x 10(6) interactions against 15 proteins. They identified and classified 170 potential interactors, including approximately 70 proteins of previously unknown function. More than 25% of the interactors are probably biologically relevant. The achievements of Fromont-Racine et al. have opened the way to the systematic analysis of the protein interaction networks of the 6,000 open reading frames-yeast proteome. This task requires, however, automation of the library screens and creation of a two-hybrid library database.

Fungal Proteins↗
PubMed1994

From Index Catalogue to Gopher space: changes in our profession as reflected in the Handbook and CPHSL.

A fifty-year review of the history of health sciences librarianship, as reflected in four editions of the Handbook of Medical Library Practice and its successor, Current Practice in Health Sciences Librarianship, illustrates the significant changes our profession has undergone. Publication in 1943 of the first edition of the Handbook marked an important milestone in the development of the Medical Library Association, as a group of dedicated volunteers documented standard practice and recorded useful data. Administration of health sciences libraries has moved from art to science. Responsibility for the development of collections is now the sole purview of professional librarians. Automation and bibliographic standards have revolutionized the methods for controlling and providing access to information resources. And, the means by which assistance is provided to library users, through the use of computer and telecommunications technology, has changed dramatically.

Cataloging↗
PubMed1999

Combinatorial biocatalysis: taking the lead from nature.

Combinatorial biocatalysis is an emerging technology in the field of drug discovery. The biocatalytic approach to combinatorial chemistry uses enzymatic, chemoenzymatic, and microbial transformations to generate libraries from lead compounds. Important recent advances in combinatorial biocatalysis include iterative derivatization of small molecules and complex natural products, regioselectively controlled libraries, novel one-pot library syntheses, process automation, and biocatalyst enhancements.

Automation↗