Peptides are arbitrarily considered as sequences of
amino acids of up to about 100 residues. Their importance in biological
processes from the most humble bacteria to the most complex mammal is beyond
doubt, having roles as diverse as neurotransmition and antibiotic activity; in
addition they function as hormones and toxins. This wide spectrum of activity
marks them out as a class of compounds of significant interest in areas from
medicinal chemistry through to molecular biology.
It is thus not
surprising that many years of effort have gone into developing suitable synthetic
methodologies. The basic principles
that lie at the heart of the subject and the most commonly used protocols are
overviewed here.
For the purpose of
peptide synthesis, amino acids can be considered as having two main
functionalities to manipulate, i.e. the
a-amino and carboxyl groups. Functional groupings are
also present in the side chains of many of the principle amino acids. These
functionalities must be protected so that they do not interfere with the
formation of the peptide bond.
With respect to
peptide bond formation there are four main steps: Protection, activation,
coupling and selective deprotection (Figure).
We will start by looking at activation and coupling, then protection and
deprotection and finally synthesis of peptides in solution and on a solid
support.
