What is a Cyclic Peptide?

Cyclic peptides are an unusual class of compounds that were first discovered from microorganisms, due to their biological activities. They range from antibiotics, such as bacitracin and polymyxnB, to the immunosuppressant drug cyclosporine. They can also be toxins. Alpha amanitin, the poison from the death cap mushroom, is also a cyclic peptide.

These compounds are undergoing very active investigation as potential new sources of drugs and antibiotics. They are much more resistant to proteases — enzymes that break down proteins — than a linear peptide chain. This resistance to proteolysis means that they tend to survive the human digestive process. They can also bind proteins in the cell where traditional drugs cannot.

The unusual properties of cyclic peptides are due both to their circular structure and their unusual mode of biosynthesis, which frequently incorporates uncommon compounds. Aside from the 20 amino acids normally used in proteins, 300 different natural compounds can be used in synthesizing cyclic peptides. For instance, they can contain D amino acids.

Like all peptides, they are comprised of chains of amino acids linked by a peptide bond. Most peptides are linear, having an N terminus with an amino group at one end, and a C terminus with a carboxyl group at the other. In cyclic peptides, the N and C ends are linked together, forming a cyclic polypeptide chain. When there are fewer than 50 amino acids, the compound is known as a cyclic peptide. A larger compound is known as a cyclic protein.

There is much research targeting the synthesis of new cyclic peptides. They can be synthesized by specialized techniques, known as peptide synthesis. There are biotechnology companies that specialize in making custom peptides for research studies. Cyclic peptides have shown promise in treating Alzheimer’s and Huntington’s diseases. As more information becomes available about their interaction with cellular proteins, it may be possible to develop even more drugs from this diverse class of compounds.

Aside from the biological activity of cyclic peptides, they are of interest as carriers. This means they can be engineered to carry drugs into the body. Particularly if the drug is a peptide, it can be synthesized as part of the cyclic peptide and taken orally.

The biosynthesis of natural cyclic peptides is interesting to biologists, since it frequently involves non-ribosomal peptide synthetases. Most peptides are made by ribosomes, which use messenger RNA (mRNA) as a template and then assemble the amino acids to form a peptide or protein. Some microorganisms have large enzyme complexes composed of modules that they use to assemble the cyclic peptides. They do not use ribosomes or mRNA. In some cases, it is possible to alter the modules and genetically engineer the cyclic peptide, possibly forming new compounds with biological activity.