Bioorganic Chemistry
25
R
1
H
2
N
N
10 possible
(1) 10 sublibraries synthesized:
10 possible 10 possible
=
1000 total peptides
N
H
OOO
OH
H
R
2
R
3
R1-N-N
R1
=
ALA
GLY
SER
THR
PRO
TYR
LY S
GLN
ARG
ASP
N
=
random mixture
of 10 amino acids
GLY-R2-N
R2
=
ALA
GLY
SER
THR
PRO
TYR
LY S
GLN
ARG
ASP
N
=
random mixture
of 10 amino acids
GLY-PRO-R3
R3
=
ALA
GLY
SER
THR
PRO
TYR
LY S
GLN
ARG
ASP
N
=
random mixture
of 10 amino acids
Winner forms
basis for second
10 sublibraries
Winner forms
basis for third
10 sublibraries
Winning compound
identified: GLY-PRO-ASP
Fig. 19
Deconvolution of the same library from Fig. 18 using the method of iterative deconvolution.
10 sublibraries would then be synthesized,
with the specifc selected amino acid From
the frst round in the frst position, 1 oF the
10 possible amino acids in the second po-
sition, and a random amino acid selected
From the third position. (See ┬▒ig. 19). This
process would continue until a single high-
activity species was identifed From the
fnal sublibrary.
Both these methods have been exten-
sively used to determine the sequence
oF active species From large combina-
torially generated mixtures. There is a
range oF other deconvolution strategies
that have been described and contrasted.
Both iterative deconvolution and positional
scanning require that some positions in a
sequence be randomized. There are two
possible ways oF doing this randomization.
The most conceptually straightForward ap-
proach is to simply use a mixture oF amino
acids when coupling to a given position.
One oF the disadvantages oF this method is
that each amino acid in a mixture will have
a diFFerent coupling rate and eFfciency,
which depends not only on itselF but on
the amino acid it is coupling to. The result
oF this is that some amino acids, iF they
are particularly reactive, can be overrep-
resented at the position. A way to avoid
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