This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
Small Molecules
What are small molecules?
Small molecules are low molecular weight organic compounds that can bind to proteins and potentially help regulate biological processes. Binding of a small molecule can alter protein shape, activity and function resulting in inactivity or new function [1]. These compounds are used in chemical genetics and are preferred over conventional genetics due to their temporary and reversible alterations to cells. Information gathered from this research can be used in the discovery and development of treatment options for a variety of diseases [2]. How do we determine what small molecules interact with what proteins? Similar to DNA microarrays, small molecule microarrays assess the binding of a known protein to thousands of small molecules organized on a slide. Once the slide is washed with the known protein, it is analyzed for fluorescent spots, signifying the binding of protein to a small molecule [3]. See how small molecule microarrays are done here. |
Small Molecules & NBN
Searches of PubChem identified 15 bioactive chemicals that target NBN. Bioactive compounds can have effects, cause a reaction, or trigger a response in living organisms or tissue [4] . Though information on these chemicals is rather scarce, one compound was found to maintains activity, 12 rendered the gene inactive, and two had unspecified outcomes. All chemicals were identified using RNAi or siRNA screens.
No targets, compounds or bioassays could be found for NBN. |
Discussion
According to PubChem and Chembank, there exists little to no information regarding small molecules interacting with NBN. However, A-T, a "sister disease" of NBS, possesses a variety of targets, compounds, bioassays and bioactive compounds in relation to its mutated protein, ATM. Because the cytogenetic phenotypes of these diseases are so similar, knowledge from ATM research could serve as a starting point in the discovery of NBN targets, compounds, and bioassays.
Further chemical genetic research for NBS needs to be preformed. The ability to utilize compounds that could enhance the activity of a mutated NBN protein could prove extremely beneficial for NBS patients, greatly reducing their predisposition to cancer. |
References:
Figure 1. http://prospect.rsc.org/blogs/cw/2009/12/10/500000-structures-and-counting/ [1] Kawasumi, M., & Nghiem, P. (n.d.). Chemical Genetics: Elucidating Biological Systems With Small-Molecule Compounds. Journal of Investigative Dermatology, 1577-1584. Retrieved from http://www.nature.com/jid/journal/v127/n7/full/5700853a.html [2] Choi, H. Kim, J. Chang, Y, Nam, H. (2013). Forward Chemical Genetic Screening. Methods in Molecular Biology, 393-404. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24057378 [3] Small-Molecule Microarrays | HHMI's BioInteractive. (n.d.). Retrieved March 27, 2015, fromhttp://www.hhmi.org/biointeractive/small-molecule-microarrays [4] Abdelkarim GUAADAOUI, Soumaya BENAICHA, Naima ELMAJDOUB, Mohammed BELLAOUI, Abdellah HAMAL. What is a Bioactive Compound? A Combined Definition for a Preliminary Consensus. International Journal of Nutrition and Food Sciences. Vol. 3, No. 3, 2014, pp. 174-179. doi: 10.11648/j.ijnfs.20140303.16 |