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Pure Appl. Chem., Vol. 71, No. 12, pp. 2349-2365, 1999

Glossary of Terms Used in Combinatorial Chemistry

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Safety-Catch Linker: A linker which is cleaved by performing two different reactions instead of the normal single step, thus providing greater control over the timing of compound release. Thus the sulfonamide resin below must first be alkylated to render it susceptible to cleavage by nucleophilic displacement 92-94.

Scaffold: Core portion of a molecule common to all members of a combinatorial library.

Scavenger Resin: solid-supported reagent which will react with undesired materials (such as excess reagents) and remove them from solution. Thus the polymer-supported amine in the example allows removal of excess isocyanate. See also sequestration-enabling reagent 95-98.


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SELEX: "Systematic Evolution of Ligands by Exponential Enrichment"; Process for identifying aptamers by iterative enrichment of oligonucleotide mixtures with respect to their ability to bind a target 4-6.

Sequestration-Enabling Reagent: Reagent which converts undesired by-products or residual starting materials into a form which may more easily be removed from reaction mixture by, for example, solid-phase extraction or other phase switch. Thus the anhydride (below) will react with residual amine to give an acidic product which is removed by salt formation with an amine scavenger resin. Excess anhydride will in turn react with, and be removed from solution by the same resin 98,99.


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Site Isolation: Property of solid supports whereby functional groups are separated from each other by the polymeric framework, and thus, while they may be physically in close proximity, reduced levels of reaction between sites may be observed. Also refered to as pseudo-dilution.

Solid-Phase Extraction: Method for sample purification whereby either the desired or undesired components of a mixture have preferential affinity for a solid material. Adding the mixture to the solid material then allows facile separation of the desired material by filtration. See also sequestration-enabling reagent and scavenger resin.

Solid Support: Insoluble, functionalized, polymeric material to which library members or reagents may be attached (often via a linker) allowing them to be readily separated (by filtration, centrifugation, etc.) from excess reagents, soluble reaction by-products, or solvents 18,100,101.

Soluble Support: An attachment, common to all library members, which renders the library components soluble under conditions for library synthesis, but which can be readily separated from most other soluble components when desired by some simple physical process. This process has been termed liquid-phase chemistry. Examples of soluble supports include linear polymers such as poly(ethylene glycol), dendrimers, or fluorinated compounds which selectively partition into fluorine-rich solvents (see fluorous synthesis) 59,102.

Sort and Combine: Use of directed sorting to facilitate library assembly. Related to pool/split protocol but more commonly applied to macroscopic solid supports (such as pins and related carriers) where each library member is found on only one, or a small number of carriers.

Spatially Addressable: Having the ability to identify at least part of the structure of a library component or pool by noting its physical location in an array 8,10.

SPE: solid phase extraction

Split/Pool: see Pool/Split

Stochastic: "Aiming, proceeding by guesswork" (Websters Collegiate Dictionary). Term which is often applied to combinatorial processes involving true random sampling, such as selection of beads from an encoded library, or certain methods for library design 103.

Sub-Library: (see also Pool) A subset of a combinatorial library, physically separate from the rest of the library, generally with one or more fixed building block.

Sub-Monomer Synthesis: Process resulting in an oligomer in which each monomer residue is formed from two or more building blocks. This approach has been used for peptoid synthesis 72.

SURF: 'Synthetic Unrandomization of Randomized Fragments'; Strategy for identifying active members of a mixture related to deconvolution and positional scanning 104.

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