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Peptide Synthesis
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Peptide Synthesis
Who or=
What
Can Synthesize Proteins?
<=
span
style=3D'font-size:88%'>• Any living cell - from DNA
<=
span
style=3D'font-size:88%;visibility:hidden'>•
<=
span
style=3D'font-size:88%'>• In vitro translation
systems - from mRNA
<=
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style=3D'font-size:88%;visibility:hidden'>•
• Chemists in a lab using peptide synthesis =
techniques
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Peptide Synthesis
Capabi=
lities
of Peptide Synthesis
•=
Can produce peptides 2-100 amino acids long
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/span>
•
•=
If these peptides are carefully combined, longer
peptides can be made
<=
/span>
•
• Can produce a large variety of modified and unusu=
al peptides that cannot be made by living systems=
3; •
•
Peptide Synthesis
Uses f=
or
Synthetic Peptides
•=
Biologically active peptides (e.g., neuropeptides=
) can
be made for receptor
studies, kinetic experiments, etc.
• =
Analogs
of biologically active peptides can be produced
– =
Allows
study of structure-function relationships
– =
Inhibitors
can be produced
– =
Used
extensively in pharmaceutical development
•=
Portions of proteins are synthesized for producti=
on of antibodies to the protein
•
•
Peptide Synthesis
Calcito=
nin
– A Regulator of Calcium
<=
span
style=3D'visibility:hidden'>•
<=
span
style=3D'visibility:hidden'>•
• ACDTATCVTHRLAGLLSRSGGVVK NNFVPTNVGSKAF
Peptide Synthesis
The
Basic Reaction - Formation of a peptide (amide ester) bond
Peptide Synthesis
Format=
ion of
a Peptide Bond
•=
For amide bond formation to occur rapidly and quantitatively, the carboxyl C must be activated&=
#13;
•=
An active=
ester of =
the amino
acid is formed
•<=
/span> The original method for doing this utilized carbodiimides; reaction of an amino acid with a carbodiimide for=
med 0- acyl
intermediates
•=
&nbs=
p;
Carbodiimide &nbs=
p;
R-N=3DC=3DN-R
Peptide Synthesis
Reactio=
n of
Carbodiimides with Amino Acids
<=
img
border=3D0 v:shapes=3D"_x0000_s20485" src=3D"slide0019_image004.gif"
style=3D'position:absolute;top:39.25%;left:7.49%;width:85.01%;height:43.7=
5%'> Peptide Synthesis
The
carbodiimide most commonly used in peptide =
synthesis is dicyclohexylcarbodiimide (DCC)
<=
img
border=3D0 v:shapes=3D"_x0000_s21509" src=3D"slide0020_image006.gif"
style=3D'position:absolute;top:42.75%;left:7.49%;width:85.01%;height:34.2=
5%'> Peptide Synthesis
DCC
can be used to couple HOBt to the amino acid This produces a =
more
strongly activated amino acid
•=
The first amino acid is reacted with DCC to produce the O- acylisourea
•<=
/span> This then reacts with HOBt to make an HOBt activated ester of an amino acid
•=
The activated ester reacts with the second amino acid
Peptide Synthesis
Formation
of Peptide Bond using DCC and HOBt
<=
img
border=3D0 v:shapes=3D"_x0000_s23557" src=3D"slide0022_image010.gif"
style=3D'position:absolute;top:25.5%;left:10.11%;width:79.77%;height:67.7=
5%'> ![](3D"slide0017_image002.gif")
![](3D"slide0021_image008.gif")