One of the most common sleep disorders is also one of the most difficult to suppress — jet lag. This is not for lack of trying: exercise, Viagra, and flashing a strobe light on your eyes have all been proposed as a cure. We’re told to drink booze and to not drink booze. These solutions, so far, have done very little to help: The World Health Organization says that jet lag can only be reduced, not prevented.

However, a discovery made by researchers at the Institute of Transformative Bio-Molecules at the Nagoya University could change everything for sleep-deprived travelers. By rapidly synthesizing the activity of circadian rhythm-changing molecules, the researchers became the first to discover and target a molecule that affects a specific circadian protein called CRY. They believe that this discovery opens the way to develop a treatment that can modify this molecule, and in turn adjust one’s circadian rhythm.

The circadian rhythm is the 24-hour biological clock that regulates the sleep and wake cycles, hormone secretion, and metabolism of animals. Disruption — whether it’s something serious like a genetic mutation or an environmental factor like taking a red-eye flight — leads to sleep disorders. At best, these disorders are an annoying part of life you can get over in a few days. At worst, disruptions to the circadian rhythm could cause obesity, cancer, and mental disorders.

That’s why this discovery is a boon for travelers and could be a life-saver for many more. But for now, the research is still in the experimental stage.

“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,” says co-author Takashi Yoshimura.

The feedback loop of the molecule KL001.

The proteins CRY and PER work in tandem with two other proteins, CLOCK and BMAL1. Together, their activation and blocking system makes up the basis of a circadian rhythm. In 2012, the same team of researchers discovered a new molecule, named KL001, which has the capability of lengthening a circadian cycle when it comes into contact with CRY. By applying C-H activation chemistry to KL001 in this current study, the team was able to synthesize over 50 derivatives of the molecule — allowing the researchers to find the critical sites on the molecule that affect rhythm-changing activities, which they believe could be manipulated to lengthen or shorten the period of the circadian rhythm.

“Our investigations reveal the possibility that there may be other CRY-mediated period-shortening regulatory mechanisms yet to be discovered,” says co-author Stephan Irle. “Through further studies, we would like to find how small changes in the molecular structure lead to opposite rhythm changing activities.”


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