Chemistry Reference
In-Depth Information
13.6 Peptide synthesis
the remaining amino and carboxyl groups to react,
provided the carboxyl group is suitably activated
to make it more reactive, as discussed above (see
Section 13.5). After coupling and formation of the
new amide bond, the product can be deprotected
to yield the dipeptide. Alternatively, one or other
of the protecting groups can be removed, allowing
the sequence to be repeated, leading to larger
peptides. This is shown in the following general
scheme.
Many different approaches have been developed for
peptide synthesis
, and it is not the intention to cover
more than the basic principles here, with a suitable
example. The philosophy to convert two amino acids
into a
dipeptide
is to transform each difunctional
amino acid into a monofunctional compound, one
of which has the amino group protected, whilst the
other has the carboxyl group protected. This allows
R
R´
H
2
N
CO
2
H
H
2
N
CO
2
H
X = activating group
Y, Z = protecting groups
protect −NH
2
R
protect
−
CO
2
H
Z
H
CO
2
H
activate −CO
2
H
add further
residues to
carboxyl end
R´
R
Z
H
2
N
CO
2
Y
H
COX
add further
residues to
amino end
couple
R
R
R
N
N
N
Z
CO
2
H
Z
CO
2
Y
CO
2
Y
H
H
H
2
N
remove −NH
2
protecting group
remove −CO
2
H
protecting group
O
R´
O
R´
O
R´
remove all
protecting
groups
R
N
CO
2
H
H
2
N
O
R´
dipeptide
13.6.1 Protecting groups
destroy the new amide bonds. Where amino acid side-
chains have carboxylic acid or amino groups, you
will readily appreciate that manipulating protecting
groups on these groups separately from those related
to making the peptide linkage can turn out to be a
highly delicate operation.
Let us consider one method to synthesize the
dipeptide Ala-Leu. It is necessary to protect the
amino group of Ala and the carboxyl group of Leu.
What is not included here is the need also to protect
any vulnerable functional groups in the amino acid
side-chains. A range of methods is available to
protect amino, carboxyl, thiol, and hydroxyl groups
and prevent them reacting during the amide bond
synthesis. Such groups also have to be removed
after their job is done, using conditions that do not
