Download Different Techniques in CC

Combinatorial Chemistry
Different techniques in
combinatorial and solid
phase chemistry
presented by: Dominik Göddertz
Table of contents
• Multiple solid phase peptide synthesis MPS
• Multipin-Technique
• Tea-Bag Method
• Parallel libraries
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Light-directed spatially addressable parallel chemical synthesis
Spot synthesis
Coupling of compound mixtures
Split and Mix synthesis
Multipin-Technique
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96 pins (40 mm long, 4 mm in diameter)
pins fit in 96-deep-well MTP
coupling takes place in wells of the plate
peptides remain on pins during the synthesis (only PG
are removed)
necessity to wash intensely after every coupling step
peptides can be removed into individual wells after
the synthesis
maximum yield 300 nmol/pin
analysis and purity control are very difficult
1984, Geysen et al
Multipin-Technique
Tea-Bag Method
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15 x 22 mm mesh packets with µm-sized
pores separates the polymeric support
greater quantity of each compound (up to
500 µmol)
complete biological and structural
characterization
disadvantage: intensity of labour
1984, Houghten
Light-directed spatially addressable
parallel chemical synthesis
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functionalized silica wafer with
covalent linker molecules
terminated with photolabile PG
light is directed through a mask
to deprotect and activate
selected sites
protected amino acids couple to
activated sites
2
40 000 sequences/cm
1991, Fodor et al
Spot-Synthesis
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peptides are synthesized on amino
functionalized cellulose paper sheets
by spotting the reagents at defined
positions
washing and deprotecting steps are
performed by dipping the paper in
corresponding solutions
2
20 sequences/cm
1992, Frank
Coupling of compound mixtures
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A
B
A
B
C
coupling of
mixtures
C
A
A
BB
C
C
ABC
20 different compounds/step
3
e.g.: 3 pos = 20 = 8000
executable with e.g. multipin, tea bag or spot
synthesis
Disadvantage:
• different coupling tendency of amino acids
1986, Geysen
Split and Mix Synthesis
Divide, Couple and Recombine
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6 reaction steps produce 9
compounds
executable with e.g. beads or
tea-bags
Literature
• A. Beck-Sickinger Kombinatorische Methoden in
Chemie und Biologie, Wiley-VCH, 1999.
• G. Jung Combinatorial Chemistry, Wiley-VCH,
1999.
• Skript zur Vorlesung Biosensorik & Screening.