Scientists created a gel that holds the hormone GnRH and releases it in bursts when you shine green light on it. This mimics the natural pulsing of the hormone, which is important for certain health effects, especially in brain health. The chemistry is unusual because they attached the hormone to the gel through a part of the molecule that isn’t normally used.

In this work, we demonstrate that the photoactivated depot (PAD) approach can be used to produce pulsatile release of human gonadotropin releasing hormone (GnRH) using green light. Pulsatile release is critical for a range of hormones and produces distinct physiological responses in comparison with continuous release. In particular, this has been observed with the use of GnRH for the treatment of cognitive impairment in Down syndrome. We have synthesized a GnRH PAD material utilizing a green light activated nonpolar tag based on the thiocoumarin photocleavable group. This material is essentially insoluble, as required of depots in the PAD approach. Upon photolysis, it releases native soluble GnRH. A major synthetic challenge for the synthesis of this PAD was that GnRH has neither of the standard functional groups previously utilized (carboxyl or amine) to link to the light-activated, solubility controlling moiety. Using proteolysis and de novo peptide sequencing, we demonstrate that GnRH is modified via the guanidino group of arginine, making an unusual linkage. We demonstrate that this material is highly stable toward chemical hydrolysis and releases pulses of soluble GnRH in response to pulses of 500 nm light.