Cyclic peptides
. In April 2012, researchers at Carnegie Mellon University reported on their manufacturing method for a synthetic form of
a cyclic peptide. Macrocyclic peptides with multiple disulfide cross-linkages, such as those produced by plants and those
found in nonhuman primates, hold potential as drugs because of their broad biological activities and high chemical, thermal,
and enzymatic stability (12). Because of their intricate spatial arrangement and elaborate interstrand cross-linkages, some
macrocyclic peptides are difficult to prepare in large quantities and high purity because of the nonselective nature of disulfide-bond
formation (12).
In the current study, the Carnegie Mellon researchers focused on RTD-1, a cyclic peptide held together by three disulfide
bonds. RTD-1 has a broad range of antibacterial, antifungal and antiviral capabilities and has been shown to inhibit HIV from
entering cells. The researchers created a mimic of RTD-1. While the outside of the mimic peptide maintained the same amino
acids as the original, the researchers replaced the disulfide bonds at its center with noncovalent Watson–Crick hydrogen bonds
without significantly affecting the biological activity of the peptide. The researchers say the work provides a general strategy
for engineering conformationally rigid, cyclic peptides without the need for disulfide-bond reinforcement (12).
They tested the efficacy of the mimic RTD-1 by mixing the peptide with Escheria coli, Listeria, Staphylococcus, and Salmonella—bacteria that RTD-1 typically protects against.
The mimic proved to be effective in killing each of the types of bacteria tested by the researchers, which included both gram-positive
and gram-negative bacterial strains. Furthermore, the mimic peptide worked by binding to the bacteria's cell membrane, not
its DNA or RNA, decreasing the probability that the bacteria could develop resistance to the peptide, according to an Apr.
13, 2012, Carnegie Mellon University press release. The researchers plan to see if the mimic RTD-1 is effective against other
types of pathogens, including antibiotic-resistant bacteria. They also plan to apply their method to manufacture mimics of
other cyclic peptides, according to the university release.
Other approaches. In 2011, the biopharmaceutical company Sutro Biopharma formed a multiyear collaboration with Pfizer for
the research, development, and commercialization of novel peptide-based therapeutics. The partnership gives Pfizer access
to peptides that have been difficult to produce using conventional technologies using a biochemical protein synthesis technology
platform developed by Sutro, In 2008, Pfizer acquired CovX, a biopharmaceutical company with a technology platform that links
therapeutic peptides to an antibody scaffold. The peptide targets the disease while the antibody scaffold allows the peptide
to remain in the body long enough to achieve therapeutic benefit. The technology thereby allows for better half-life extension
and bioavailability to support optimal dosing regimens for peptide therapeutics.
Patricia Van Arnum is executive editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, pvanarnum@advanstar.com
. Twitter@PharmTechVArnum
References
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