Glossary of Terms Used in Combinatorial
Chemistry
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S
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.
