Cyclic peptides (CPs) are a type of small molecule with a circular sequence of bonds. They are used to modulate the activity of RNA and can bind to an RNA of interest. This allows for the temporal regulation of gene expression. A wide variety of cyclic peptides are in use as therapeutics. Some of these peptides are hormone analogues, antibiotics, fungal infections, and even oncology drugs.
The structure of cyclic peptides has shown great promise in drug research. In fact, many of these compounds have already been approved as drugs in the U.S. and around the world. However, there are several challenges facing their development. As a result, scientists have explored a number of ways to enhance cyclic peptides’ bioavailability.
One of the most prominent methods is to change the amide backbone of a cyclic peptide. This is known as N-methylation. It changes the number of hydrogen bond donors. If the peptide amide is modified, it will have a different membrane permeability.
Another method is to change the steric constraints of the peptide. In the case of macrocycles, the side chains are replaced with propionic residues. These compounds have better membrane permeability and pharmacokinetic properties.
Researchers also have found that cyclic peptides can cross membranes more readily than their linear counterparts. Cyclic d,l-a-peptides have been used to kill Gram-positive bacteria.
Cyclic peptides are among the most promising PPI modulators. Despite their success, however, they still face several challenges. For instance, oral availability and cell permeability are two major obstacles.