New molecules created with synthetic chemistry can alter the circadian rhythm in mammals. Chemists and biologists at the Institute of Transformative Bio-Molecules (ITbM) at Nagoya University in Japan have reported the first circadian period-shortening molecule targeting the clock protein, CRY, in Angewandte Chemie International Edition, The study, also reported in Medical News Today, demonstrates the ability of synthetic chemistry "to rapidly synthesize and tune the activity of circadian rhythm-changing molecules" (http://www.medicalnewstoday.com/releases/295096.php).
According to the Sleep Foundation, the human circadian biological clock regulates the timing of periods of sleepiness and wakefulness throughout the day. A person's circadian rhythm dips and rises at different times of the day. The sleepiness people experience during these circadian dips is less intense for people who have had sufficient sleep and more intense for those who are sleep deprived. Additionally, the circadian rhythm makes people feel more alert at certain times of the day, even if they have been awake for long periods of time and their sleep/wake restorative process could make them feel more sleepy (http://sleepfoundation.org/sleep-topics/sleep-drive-and-your-body-clock).
The Medical News Today article goes on to explain that most living organisms have "a biological clock with an approximately 24-hour circadian rhythm, which regulates important body functions such as sleep/wake cycles, hormone secretion and metabolism." That cycle can be disrupted by genetic mutations and environmental factors, including jet lag and unusual work shifts, as well as diseases such as sleep disorders, obesity, cancer and mental illness.
According to Tsuyoshi Hirota, a chronobiologist and an associate professor at ITbM, there are very few molecules directly act on clock proteins and control the circadian clock in mammals. The research team used synthetic chemistry to synthesize and adjust the activity of circadian rhythm-changing molecules. They determined critical sites on the molecules for bioactivity and used period-lengthening/-shortening molecules to ascertain the way in which the clock protein is regulated by the body's timekeeping mechanism. The results of this study could help to develop additional molecules that can control the circadian rhythm in mammals. Such molecules could be used to prevent circadian-related diseases and manipulate ciccadian-dependent reproductive activity in animals to provide solutions for food production.
Takashi Yoshimura, an animal biologist and professor at ITbM, who led this research from a biological perspective, concluded, "We hope we can make further use of synthetic chemistry to make bioactive molecules that can control the circadian rhythm of animals and gain further insight into the circadian clock mechanism, which will surely contribute to medical applications, food production and advances in clock research. This has been a wonderful experience for me to work with chemists and we will continue to work together for more exciting results to come."
