COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES

Classification Context

Section:

CHEMISTRY; METALLURGY

Class:

COMBINATORIAL TECHNOLOGY

Subclass:

COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES

Scope Notes

Glossary: Array arrays Set of compounds maintained in a specified spatial distribution e.g. in the wells of a 96-well plate, in pins held in a rack or at the tip of optical fibers arranged in a bunch. Biochemical method biochemical methods Process involving the use of microorganisms, enzymes, vectors or antibodies. Chemical Evolution Process Process using in vitro selection systems that evolve to enrich mixtures of chemical compounds in those components having selected properties. The terminology "directed molecular evolution" is commonly employed when the process is applied to mixtures of macromolecules (e.g. RNA aptamers). Selected compounds are then amplified ("copied") using biochemical methods (e.g. enzymatic reverse transcription of RNA aptamers to DNA, PCR amplification and finally retranscription to RNA); This concept has been adapted to organic chemistry and opened a new branch of combinatorial chemistry named "dynamic combinatorial chemistry" wherein the enrichment in the (usually low-molecular weight) compounds having a selected property results from the equilibration process that carries out a preferential destruction and recycling of unselected compounds. Coding/encoding Coding encoding Strategy whereby a surrogate analyte is associated with each member of a library in order to record its structure and/or the reaction sequence used for its preparation. This is usually achieved by the use of tags/labels attached to the particles of solid support on which the library members are assembled. Combinatorial library Combinatorial libraries A set of compounds (a library) prepared by combinatorial synthesis. May consist of a collection of pools or sub-libraries. Combinatorial synthesis Combinatorial synthesis is the preparation of sets of diverse entities by the combination of sets of chemical building blocks, e.g. reagents. Contained in A library contained in a microorganism, a cell or a vector is a library the members of which are present in the respective biochemical, e.g. in a plasmid. Decoding Method enabling the determination of the structure of a library member and/or the reaction sequence leading to its preparation, consisting in "reading" (e.g. determining the structure of) a surrogate analyte (code, tag, label) associated with said library-member. Deconvolution Process consisting of fractionating (normally by resynthesis, or by elaborating a partial library) a pool with some level of the desired activity to give a set of smaller pools. See also iterative deconvolution. Directed Molecular Evolution Directed Molecular Evolution is a process for enriching a library in members having a property or activity of interest. It involves cycles of taking a library, subjecting it to a screen to select for the desired property or activity, amplifying the "hits" to provide the starting library for the subsequent cycle. "Mutations" may be introduced at the amplification stage in order to increase the diversity of the library. This subject matter involves aspects of creating and screening libraries. Displayed by A library displayed by a microorganism is a library present at the surface of such a microorganism, e.g. of a bacteria. See for example Nature Biotechnology (1997), 15, pages 29-34: "Display of heterologous proteins on the surface of microorganisms: from the screening of combinatorial libraries to live recombinant vaccines. Dynamic Library Collection of compounds (in solution) in dynamic equilibrium (i.e. constantly changing). If the composition of the library is altered by the presence of a target which selectively binds certain library members, then shifting of the equilibrium will lead to an increase in the amount of those components which bind to the target with relatively high affinity. A dynamic library contains all the potentially possible combinations of the components undergoing dynamic random connection, whether these combinations are or are not actually present in the conditions used. It is a virtual library. A real entity is generated in the presence of the target. Fluorous Synthesis Approach for solution phase synthesis which takes advantage of the ability of highly fluorinated groups to partition out of aqueous and most organic solutions into a third phase consisting in a fluorinated solvent. The fluorinated side chain can act as a soluble support for synthesis. Identifying Determining the exact nature, e.g. chemical structure or sequence listing, of a particular library member or of a particular subset of library members. In silico library A library which has no physical existence, being constructed solely in electronic form or on paper. It is one type of virtual library. The building blocks required for such a library may not exist, and the chemical steps for creating such a library may not have been tested. These libraries are used in the design and evaluation of possible libraries. "Integrated" apparatus Integrated apparatus Apparatus specifically designed for performing at least two different operations, e.g. synthesis and screening. Iterative deconvolution Method for the identification of active library members consisting in repeating the deconvolution strategy a certain number of times. Usually the initial library is divided into non-overlapping subsets. The subsets are tested (screened) separately, and the one with the greatest activity is identified. This subset is re-synthesised as a collection of simpler subsets which are tested for activity. The process is repeated until a unique library-member with (ideally) a high level of activity is identified. Library Libraries A library is a created collection of a plurality of compounds, microorganisms or other substances. The collection is useful as a test vehicle for determining which of its members or its subsets of members possess activities or properties of interest. A library might for example exist as: a solution; a physical admixture; an ordered or unordered array; a plurality of members present on a support and affixed thereto, e.g. by chemical bonding, by physical attractive forces or by coating. Liquid-phase synthesis Liquid phase synthesis In the context of , this wording covers both solution phase syntheses (i.e. reactions involving only one liquid phase) as well as syntheses in multiple liquid phase systems (i.e. involving more than one liquid phase). The latter concern for instance syntheses performed on a liquid macromolecular compound such as PEG (polyethylene glycol), on dendrimers, or wherein a fluorocarbon phase is present in the system (fluorous synthesis). Microorganisms microorganism bacteria, actinomycetales, fungi (e.g. yeast), virus, human, animal, or plant cells, tissues, protozoa or unicellular algae. Particular attachment method Particular attachment methods particular method of attachment particular methods of attachment Specific method of attachment focusing on the way molecules are bound to the solid or liquid support, e.g. by means of electrostatic interactions, formation of covalent bonds by cycloaddition reactions or by irradiation. Resin capture Method consisting in contacting the reaction medium with a solid support after a reaction performed in solution, in order to attach the reaction product to the resin and thus collect it easily. Safety-Catch Linker safety-catch linkers A linker which is cleaved by performing two different reactions instead of only one, thus providing greater control over the timing of compound release. In practice, the resin is "activated" before the actual cleavage takes place (e.g. cleavage by nucleophilic displacement of a previously alkylated sulfonamide resin). Screening Determining whether a library contains a member or members which have a particular property or activity of interest. Solid-phase synthesis Solid phase synthesis Synthetic process wherein the reactions are performed on a solid support, usually in the presence of a solvent, i.e. wherein one or more library building blocks are bound to a solid support (e.g. polymer, resin, glass beads) during library creation. Solid support solid supports Insoluble, functionalised, polymeric material to which library members or other reagents may be attached (often via a linker) allowing library members to be readily separated (by filtration, centrifugation, etc.) from excess reagents, soluble reaction by-products or solvents. Solution-phase synthesis Solution phase synthesis Solution Synthesis performed in solution, i.e. wherein the reactants and reagents are all soluble in the reaction medium (irrespective of the fact that, for instance, a supported catalyst is used during the reaction). It is also called "synthesis in solution". Traceless Linker traceless linkers Linker which does not leave any residue on the cleaved compound, i.e. which is replaced by a hydrogen atom. Virtual library A library which has no physical existence. This terminology encompasses two different types of libraries: in silico libraries and dynamic libraries. | Limiting references: In silico combinatorial libraries of nucleic acids, proteins or peptides In silico combinatorial chemistry

Related Keywords

Child Classifications

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• C40B 10/00 Directed molecular evolution of macromolecules, e.g. RNA, DNA or proteins
• C40B 20/00 Methods specially adapted for identifying library members
• C40B 30/00 Methods of screening libraries
• C40B 40/00 Libraries , e.g. arrays, mixtures
• C40B 50/00 Methods of creating libraries, e.g. combinatorial synthesis
• C40B 60/00 Apparatus specially adapted for use in combinatorial chemistry or with libraries
• C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or barcodes
• C40B 80/00 Linkers or spacers specially adapted for combinatorial chemistry or libraries, e.g. traceless linkers or safety-catch linkers
• C40B 99/00 Subject matter not provided for in other groups of this subclass