Coming Down the Pike: Chaperones - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Coming Down the Pike: Chaperones


Pharmaceutical Technology
Volume 32, Issue 11, pp. 24

The analogy is often made comparing proteins with machines. It's an apt analogy, and like a bent or twisted machine, a misshapen protein is unable to function properly. Proteins are long chains of amino acids, folded into a certain configuration that allows them to perform a mechanical function. When they're folded incorrectly, they perform that function poorly or not at all, and that malfunction can lead to disease.

In humans, for example, misfolded proteins lay at the heart of diseases such as phenylketonuria (PKU) and cystic fibrosis. Many of these diseases have genetic origins, and much research has focused on correcting the gene. An alternative approach may be to look for an agent that can restore a protein to its proper shape. This approach might, in theory, also restore the protein's function.

Indeed, in nature, molecules called "chaperones" facilitate correct protein folding. Angel Pey and colleagues at the University of Bergen in Norway, the Universidad de Zaragoza in Spain, the Biocomputation and Complex Systems Physics Institute also in Zaragoza, and the University of Zurich in Switzerland, tested a panel of chemicals to see whether any would act like chaperones and restore the shape and function of the protein phenylalanine hydroxylase (PAH), the protein when misfolded leads to PKU.

In a report in the Journal of Clinical Investigation, the team reports that several chemicals showed evidence of improving activity in animal models. It remains to be seen whether these particular compounds can be developed into drugs. But the larger message for drug developers is that it may be worthwhile to look for drugs with chaperone-like activity when trying to reverse the symptoms of genetically determined diseases.

Source: A.L. Pey et al., "Identification of Pharmacological Chaperones as Potential Therapeutic Agents to Treat Phenylketonuria," Jrnl. of Clin. Invest. 118, 2858–2867 (2008).

ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

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

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
23%
Oversee medical treatment of patients in the US.
14%
Provide treatment for patients globally.
7%
All of the above.
47%
No government involvement in patient treatment or drug development.
9%
Jim Miller Outsourcing Outlook Jim MillerOutside Looking In
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAdvances in Large-Scale Heterocyclic Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler New Era for Generic Drugs
Sean Milmo European Regulatory WatchSean MilmoTackling Drug Shortages
New Congress to Tackle Health Reform, Biomedical Innovation, Tax Policy
Combination Products Challenge Biopharma Manufacturers
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
Source: Pharmaceutical Technology,
Click here