Peptides Gain Traction in Drug Development - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Peptides Gain Traction in Drug Development
Peptides and related technologies to are starting to improve production.


Pharmaceutical Technology
Volume 36, Issue 6, pp. 42-43, 62

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,
. Twitter@PharmTechVArnum

References

1. T. Sawyer, Chem. Biol. Drug. Des. 73 (1), 3–6 (2009).

2. W. Wolfson, Chem. & Biol. 16 (9), 910–911 (2009).

3. Peptide Therapeutics Foundation, Development Trends for Peptide Therapeutics Report (San Diego, 2010).

4. FDA, Copaxone Label (Feb. 27, 2009), Drugs@FDA, accessed May 15, 2012.

5. FDA, Lupron Label (Mar. 28, 2012), Drugs@FDA, accessed May 15, 2012.

6. FDA, Zoladex Label (Jan. 14, 2011), Drugs@FDA, accessed May 15, 2012.

7. FDA, Sandostain Label (Mar. 23, 2012), Drugs@FDA, accessed May 15, 2012.

8. FDA, Byetta Label (Oct. 19, 2011), Drugs@FDA, accessed May 15, 2012.

9. FDA, Forteo Label (July 26, 2009), Drugs@FDA, accessed May 15, 2012.

10. P. Van Arnum, Pharm. Technol. 35 (5), 56–60 (2011).

11. S. Bhattacharya et al., Biopolymers 97 (5), 253–264 (2012).

12. Ly et al., J. Am. Chem. Soc. 134 (9), 4041–4044 (2012).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
27%
Attracting a skilled workforce
27%
Obtaining/maintaining adequate financing
14%
Regulatory compliance
32%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Report: Pfizer Makes $101 Billion Offer to AstraZeneca
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Source: Pharmaceutical Technology,
Click here