Image of Michael Riehle, a vector biologist at the University of Arizona, who conducts mosquito research focusing on mosquito physiology. He is smiling at the camera against a green background and is wearing a blue collared shirt.
Michael Riehle, a vector biologist at the University of Arizona, studies mosquito physiology and methods to control malaria and arboviral diseases.
Michael Riehle

Mosquitoes not only ruin summer evenings but also spread life-threatening diseases. With increasing resistance to current insecticides, scientists searched for new vulnerabilities in these insects. Michael Riehle, a vector biologist, and John Jewett, a biochemist, both at the University of Arizona, aimed for a unique target: mosquito larvae’s guts.

The gut environment in mosquito larvae transitions from high to neutral pH during digestion. Leveraging these unique chemical conditions, Jewett developed a pH-sensitive probe to tag, modify, and eventually add toxic compounds to break down gut proteins. Their findings, published in the Journal of the American Chemical Society, may aid in developing more effective mosquito control solutions.1

“There are many organisms with neutral environments like adult mosquitoes, but you lose the specificity of targeting just this environment,” remarked Riehle.

To overcome this problem, the team developed a probe using an aryl diazonium ion—a triple-bonded nitrogen group on an aromatic ring—bound to a protective five-membered, nitrogen-containing cyclized compound. They added the chemical probes to the larval feed water, where the five-membered ring group detached under alkaline midgut conditions and released the aryl diazonium ion. 

Image of John Jewett, a biochemist at the University of Arizona, who works on reactive probes designed to be released in biological environments. He is smiling at the camera and is wearing a pair of black glasses and a black shirt.
John Jewett, a biochemist at the University of Arizona, works on reactive probes designed to interrogate challenging biochemical environments.
Trianna Oglivie

Then, the ion nonspecifically bound to gut proteins at neutral pH without causing acute toxicity. By tagging the probe’s terminal alkyne with fluorescent markers through a copper click reaction, the team confirmed that pH-responsive compounds broadly targeted gut proteins; control probes did not affect midgut proteins.

"[This study] is a great example of how we can identify unique biological conditions and different targets for chemists to design molecular mechanisms to exploit,” said James Checco, a chemical biologist at the University of Nebraska-Lincoln who was not involved in the study. 

The team is excited about the probe’s versatility. Jewett noted, “We’ve certainly made a lot more different derivatives of [these compounds].” Riehle added, “[Our system] will allow us to attach a variety of potentially toxic compounds, providing flexibility for mosquito larval control.”

  1. Guzmán LE, et al. J Am Chem Soc. 2024;146(12):8480-8485.