6.3 Encoding methods
A wide variety of encoding methods have been developed to record the history
of a bead used in the Furka mix and split technique. This section outlines some
of these methods.
6.3.1 Sequential chemical tagging methods
Sequential chemical tagging methods uses specific compounds (tags) as a code
for the individual steps in the synthesis. These tag compounds are sequentially
attached in the form of a polymer-like molecule to the same linker or bead as the
library compound at each step in the synthesis (Figure 6.10). The amount of tag
used at each step must be strictly controlled so that only a very small percentage
of the available linker functional groups are occupied by a tag. At the end of the
synthesis both the library compound and the tag compound are liberated from
the bead. The tag compound must be produced in a sufficient amount to enable
it to be decoded to give the history and hence the possible structure of the library
compound.
Compounds used for tagging must satisfy a number of criteria:
1. the concentration of the tag should be just sufficient for its analysis, that is,
the majority of the linkers should be occupied by the combinatorial synthesis;
2. the tagging reaction must take place under conditions that are compatible
with those used for the synthesis of the library compound;
3. it must be possible to separate the tag from the library compound and
4. analysis of the tag should be rapid and accurate, using methods that could be
automated.
Key:
Building block
A
B
CA−B−C−B−C−etcR−S−T−S−T−etc Code compoundLibrary compoundResin
beadLinkerR
S
TCode compoundFigure 6.10 Chemical encoding of resin beads. Branched linkers, with one site for attaching the
library compound and another for attaching the tag, are often used for encoding
ENCODING METHODS 123