Introduction
Chemical genetics is the process of using various chemicals to examine the effects on the phenotype in question. As would be expected, this technique is commonly used in the discovery of novel drugs to treat diseases. These assays are not usually done in a "blind" manner, but rather use a targeted approach. Chemists will identify compounds likely to interact with the mechanism of interest, and then synthesize a variety of compounds with a similar structure. Often this will result in a panel of compounds being tested, each with a certain functional group, but with different side chains or other slight variations. Blind assays can be done, but represent a higher risk on the part of the researcher, as there is less likely to be any useful results.
|
Figure 1: A representation of the general workflow of a chemical genetics assay.
|
Results and Discussion
After searching several databases of chemical genetics studies to find results pertinent to HGD and alkaptonuria, I found no results. This is unfortunate, but somewhat predictable. Because alkaptonuria is caused by a variety of defects causing total dysfunction of a relatively simple protein, it would be difficult for a small molecule to have a rescue effect.
That isn't to say that drugs may be ineffective in alkaptonuria. Nitrinisone, as mentioned on the home page of the website, is a drug that inhibits an enzyme higher up in the tyrosine/phenylalanine breakdown pathway that would prevent a buildup of homogentisic acid. However, the drug would cause a buildup of tyrosine in the blood and this side effect's severity is not fully understood [1].
That isn't to say that drugs may be ineffective in alkaptonuria. Nitrinisone, as mentioned on the home page of the website, is a drug that inhibits an enzyme higher up in the tyrosine/phenylalanine breakdown pathway that would prevent a buildup of homogentisic acid. However, the drug would cause a buildup of tyrosine in the blood and this side effect's severity is not fully understood [1].
References:
[1] Ranganath, L. R., Jarvis, J. C., & Gallagher, J. A. (2013). Recent advances in management of alkaptonuria (invited review; best practice article). Journal of Clinical Pathology, 66(5), 367-373. doi:10.1136/jclinpath-2012-200877 |
Image references:
Header: https://s-bio.com/wp-content/uploads/P6270061-crop1.jpg Fig 1: Lenci, E.; Guarna, A.; Trabocchi, A. Diversity-Oriented Synthesis as a Tool for Chemical Genetics. Molecules 2014, 19, 16506-16528. |