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Library Design (library + design)

Distribution by Scientific Domains
Chemistry88%

Selected Abstracts

Current Status of Virtual Combinatorial Library Design

MOLECULAR INFORMATICS, Issue 7 2005
Lutz Weber
Abstract Combinatorial compound libraries have become an established research tool for finding molecules with desired properties. This review gives an overview on the current status of methods, techniques and design processes for combinatorial libraries. Recent developments include the sequential and parallel use of multiple sophisticated design criteria to select suitable molecules. Diversity measures, physico-chemical and pharmaco-kinetic properties, together with a variety of target and ligand based design methods are being integrated into a seamless process. The proper choice and the implementation of design and selection tools has become a combinatorial problem by itself. However, the application of virtual library design has already yielded an astonishing increase in research productivity and is expected to become a leading tool especially for the discovery of new small molecule drug candidates in the next years. [source]

Mechanism-Guided Library Design and Dual Genetic Selection of Synthetic OFF Riboswitches

CHEMBIOCHEM, Issue 14 2009
Norihito Muranaka Dr.
Abstract After the recent discovery of bacterial riboswitches, synthetic riboswitches have been engineered by using natural and artificial RNA aptamers. In contrast to natural riboswitches, the majority of synthetic riboswitches in bacteria reported to date are ON switches that activate gene expression in response to the aptamer ligand. In this study, we adopted a mechanism-guided approach to design libraries predisposed to contain OFF riboswitches that respond to thiamine pyrophosphate (TPP). The first library design exploited a pseudo-Shine-Dalgarno (SD) sequence located near the 3,-end of the TPP aptamer, which would be less accessible to the ribosome when the aptamer is bound to TPP. In the second library, an SD sequence was strategically placed in the aptamer's P1 stem, which is stabilized upon ligand binding. OFF riboswitches were obtained by dual genetic selection of these libraries. The results underscore the importance of effective library design to achieve desired riboswitch functions. [source]

Design and Synthesis of a Focused Library of Novel Aryl- and Heteroaryl-Ketopiperazides

ARCHIV DER PHARMAZIE, Issue 12 2004
Matthias Gerlach
Abstract 1-Phenyl-4-piperazinyl-carbonyl-substituted nitrogen-containing heterocycles were discovered at Zentaris as a new class of potent, synthetic, small molecule tubulin inhibitors with strong antiproliferative activity. The lead structure of this class, D-24203, proved to be a potent inhibitor of in vivo tumor growth in different xenograft models including mammary and renal cancers. As part of our efforts in the lead optimization process to expand structural diversity as well as to optimize bioavailability parameters such as solubility and metabolic stability for these compounds, we produced and evaluated a focused library containing 320 compounds. Five new heterocyclic compound classes with comparable activity properties in the cytotoxicity and tubulin polymerization assay could be identi fied. In silico calculated bioavailability parameters for selected library members provides new compound classes with improved solubility properties. Library design, development of adequate solution phase methodology, and synthesis will be presented, as well as results of lead optimization. [source]

The new CCP4 Coordinate Library as a toolkit for the design of coordinate-related applications in protein crystallography

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 12-1 2004
E. B. Krissinel
The new CCP4 Coordinate Library is a development aiming to provide a common layer of coordinate-related functionality to the existing applications in the CCP4 suite, as well as a variety of tools that can simplify the design of new applications where they relate to atomic coordinates. The Library comprises a wide spectrum of useful functions, ranging from parsing coordinate formats and elementary editing operations on the coordinate hierarchy of biomolecules, to high-level functionality such as calculation of secondary structure, interatomic bonds, atomic contacts, symmetry transformations, structure superposition and many others. Most of the functions are available in a C++ object interface; however, a Fortran interface is provided for compatibility with older CCP4 applications. The paper describes the general principles of the Library design and the most important functionality. The Library, together with documentation, is available under the LGPL license from the CCP4 suite version 5.0 and higher. [source]

Computational challenges in combinatorial library design for protein engineering

AICHE JOURNAL, Issue 2 2004
Gregory L. Moore
[source]

Current Status of Virtual Combinatorial Library Design

MOLECULAR INFORMATICS, Issue 7 2005
Lutz Weber
Abstract Combinatorial compound libraries have become an established research tool for finding molecules with desired properties. This review gives an overview on the current status of methods, techniques and design processes for combinatorial libraries. Recent developments include the sequential and parallel use of multiple sophisticated design criteria to select suitable molecules. Diversity measures, physico-chemical and pharmaco-kinetic properties, together with a variety of target and ligand based design methods are being integrated into a seamless process. The proper choice and the implementation of design and selection tools has become a combinatorial problem by itself. However, the application of virtual library design has already yielded an astonishing increase in research productivity and is expected to become a leading tool especially for the discovery of new small molecule drug candidates in the next years. [source]

Better library design: data-driven protein engineering

BIOTECHNOLOGY JOURNAL, Issue 2 2007
Javier F. Chaparro-Riggers
Abstract Data-driven protein engineering is increasingly used as an alternative to rational design and combinatorial engineering because it uses available knowledge to limit library size, while still allowing for the identification of unpredictable substitutions that lead to large effects. Recent advances in computational modeling and bioinformatics, as well as an increasing databank of experiments on functional variants, have led to new strategies to choose particular amino acid residues to vary in order to increase the chances of obtaining a variant protein with the desired property. Strategies for limiting diversity at each position, design of small sub-libraries, and the performance of scouting experiments, have also been developed or even automated, further reducing the library size. [source]

Mechanism-Guided Library Design and Dual Genetic Selection of Synthetic OFF Riboswitches

CHEMBIOCHEM, Issue 14 2009
Norihito Muranaka Dr.
Abstract After the recent discovery of bacterial riboswitches, synthetic riboswitches have been engineered by using natural and artificial RNA aptamers. In contrast to natural riboswitches, the majority of synthetic riboswitches in bacteria reported to date are ON switches that activate gene expression in response to the aptamer ligand. In this study, we adopted a mechanism-guided approach to design libraries predisposed to contain OFF riboswitches that respond to thiamine pyrophosphate (TPP). The first library design exploited a pseudo-Shine-Dalgarno (SD) sequence located near the 3,-end of the TPP aptamer, which would be less accessible to the ribosome when the aptamer is bound to TPP. In the second library, an SD sequence was strategically placed in the aptamer's P1 stem, which is stabilized upon ligand binding. OFF riboswitches were obtained by dual genetic selection of these libraries. The results underscore the importance of effective library design to achieve desired riboswitch functions. [source]

Target-Family-Oriented Focused Libraries for Kinases,Conceptual Design Aspects and Commercial Availability

CHEMBIOCHEM, Issue 3 2005
Olaf Prien Dr.
Tailor-made libraries may increase the likelihood of identifying potential lead candidates in early drug-discovery phases. That at least 12 commercial vendors offer their services in providing compound collections of tentative kinase inhibitors reflects the growing interest in kinases within the pharmaceutical industry. Some conceptual design approaches for focused library design for the kinase family are reviewed, and the design concepts of these commercialized libraries is discussed. [source]