Chemistry Reference
In-Depth Information
8.5.3 Synthetic Methods for the Preparation of Polypeptides
Studies of protein structures and their functions in nature or mode of actions, as in the case of
enzymes, are only part of various investigations. Much effort is also put into syntheses of different
polypeptide. Such polymers can actually be formed from mixture of various amino acids by simply
heating them together. The products, however, are complex polymeric materials with random
distribution of amino acids and do not resemble any naturally occurring materials.
Base catalyzed ring opening polymerization reactions of
N
-carboxy-
-amino acid anhydrides also
a
result in formations of polypeptides:
O
H
O
R
H
N
N
base
O
CO
2
+
R
R
O
R
(for the mechanism of reaction see Chap.
5
)[
48
]. Over the years, many polypeptides were
synthesized by this reaction. These, however, were homopolymers of individual amino acids.
Copolymerization leads only to block copolymers. Ability to form random copolymers with con-
trolled sequences of amino acids, which would match naturally occurring proteins, appears to be
beyond reach by this reaction [
49
,
50
].
Duplication of naturally occurring polypeptides is needed, however, to understand the details of
structures that lead to biological activities. One of the early works consisted of assembling 23 amino
acids to form synthetic pig corticotropin [
43
]. The molecules were built stepwise [
43
].
One technique used in these syntheses is to protect the terminal amino nitrogen by forming
protective derivatives that can subsequently be easily cleaved. This is often done by converting
them to amide groups:
H
R
OCl
+
O
N
COOH
H
2
N
COOH
O
O
R
p
-Toluenesulfonyl chloride is used in the same manner. It is also possible to form imides by reactions
with phthalic anhydride:
R
O
O
R
N
COOH
O
+
H
2
N
COOH
O
O
The condensations can be carried out by a number of different techniques [
26
,
28
]. A few of them
will be shown below. One is to carry out amino acyl halide reactions:
H
H
O
SOCl
2
or PCl
5
O
N
COOH
ON
Cl
O
R
O
R
