Presentacin de PowerPoint

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Customizable Solid-Phase Peptide Synthesis
Fernando Albericio
19th American Peptide Symposium San Diego
(California) June 19, 2005
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Peptides, A Golden Age?
Talk Between Two Drugs
Drug 1
My virtues are small size, low price, oral
availability, ability to cross membranes, and
straightforward synthesis
Drug 2
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Peptides, A Golden Age?
Talk Between Two Drugs
Small Molecule
My virtues are small size, low price, oral
availability, ability to cross membranes, and
straightforward synthesis
Peptide
V. Marx, C EN, March 14, 2005
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Peptides, A Golden Age?
Peptides as Drugs Today
More than 40 marketed peptides worldwide 270
peptides in clinical trials 400 peptides in
advanced preclinical phases
Frost Sullivan report
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What is our Goal as Peptide Chemists?
To develop efficient and scaleable up strategies
for everytime more complex peptides required
How Peptides are Synthesized?
Laboratory Solid-Phase
Industrially Solid-Phase and Solution
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Solid-Phase Peptide Synthesis
1960-1980s
Bzl
Boc
PS
1980-2000s
Graft Resins
tBu
PEG-PS
Fmoc
CLEAR
All(oc)
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Solid-Phase Peptide Synthesis Program

• Solid Supports
• Handles
• Protecting (Temporal and Permanent) Groups
• Coupling Reagents
• C-Terminal Modified Peptides
• Depsipeptides

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Solid-Phase Peptide Synthesis Program

• Solid Supports
• Handles
• Protecting (Temporal and Permanent) Groups
• Coupling Reagents
• C-Terminal Modified Peptides
• Depsipeptides

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Amphiphilic (PEG) Supports
ChemMatrix
VersaMatrix

• f 0.5-0.8 mmol/g
• It is delivered dried

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Synthesis of H-(Ala)10-Val-OH by ChemMatrix and
PS resin
- 5Ala
- 4Ala
PS
- 2Ala
H-(Ala)10-Val-OH
- 3Ala
- 1Ala
ChemMatrix
H-(Ala)10-Val-OH
ABI 434 HCTU-DIEA
- 1Ala
- 2Ala
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Synthesis of BACUMA (38aa) using PS resin
MALDI-TOFF
HPLC
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Synthesis of BACUMA (38aa) using ChemMatrix resin
MALDI-TOFF
HPLC
ABI 434 HCTU-DIEA
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Synthesis of a 21 aa (Arg)n Peptide PS vs
ChemMatrix
PS
ChemMatrix
ABI 434 HCTU-DIEA
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