Carbohydrates play an important role in a broad spectrum of physiological as well as pathological processes. For example, polysaccharides on the surface of tumor cells or pathogens are possible points of attack for therapeutic drugs or vaccinations. However, the synthesis of carbohydrate-based drugs or vaccines has proven to be very complex. In addition, these are not easily absorbed into the body and decompose far too quickly.
Cyclopeptides (short ring-shaped protein chains) called glycomimetics, which imitate polysaccharides in form and consequently in function, could be a useful alternative. They are easy to produce, relatively stable, and easily absorbed.
A team of researchers at the Universities of Bielefeld and Hamburg (Germany) has now produced cyclopeptides that imitate the HNK-1 carbohydrate from human natural killer cells. HNK-1 is involved in many developmental biological processes of the nervous system. It boosts motor neuron axon growth, the growth of the fibers of muscle nerve cells. HNK-1 is found along the routes used by nerve fibers after an injury to peripheral nerves.
As a first step, the researchers led by Norbert Sewald (Bielefeld) and Melitta Schachner (Hamburg) combed through a very large number of linear peptide chains with random amino acid sequences, searching for peptides that could be recognized by HNK-1 antibodies. Starting with the sequences of two such peptides, they synthesized a series of different cyclic hexapeptides. Their trick was to replace one L-amino acid in each cyclopeptide with its corresponding D-amino acid. L-amino acids are the form that occurs in nature, D-amino acids are their mirror image. Whereas a "normal" cyclic hexapeptide is very flexible, constantly changing its spatial structure, a D-amino acid component stabilizes one preferred conformation of the ring. The peptide "presents" its functional groups of atoms in a predictable three-dimensional arrangement that is further determined by the positi
'"/>
Contact: Norbert Sewald
norbert.sewald@uni-bielefeld.de
49-521-106-2051
John Wiley & Sons, Inc.
14-Sep-2006