Dual Action
New Chemical Method Turns Proteins into Multifunctional Therapeutics
Researchers at the Max Planck Institute for Polymer Research in Mainz, together with teams from the Universities of Ulm and Lisbon, have developed a new chemical method that enables proteins to be modified quickly, precisely, and flexibly for medical applications.
With this method, two distinct functions can be attached to a single protein at the same time, for example, a drug for therapy and a fluorescent dye for medical imaging or diagnostic purposes. This opens new avenues for developing so-called biotherapeutics, medications based on naturally occurring molecules like antibodies that can act precisely within the body.
How does it work?
At the core of this method is a new class of chemical building blocks known as N-alkylpyridinium reagents. These reagents bind very selectively to a specific site on a protein, specifically, to the amino acid cysteine, which acts like a “chemical handle.”
These reagents are easy to produce, water-soluble, and environmentally friendly. Most importantly, they make it possible to attach two new functions to a protein at the same time, a major advancement over previous approaches.
“We see great potential for medicine,for example, in creating improved drugs that both act therapeutically and can be visualized inside cells or the body,” say Prof. Tanja Weil and Dr. Seah Ling Kuan, lead researchers of the study.
Real-world example: Delivering proteins into cancer cells
The method was successfully tested using a bacterial protein (the C3 toxin from Clostridium botulinum), which normally cannot enter cancer cells. After it was chemically modified with a cancer cell -targeting peptide and a fluorescent dye, the protein could be delivered into cancer cells, where it showed biological activity and could also be visually tracked under a microscope.
“Combining two functions, such as cell imaging or diagnostics and therapy into a single molecule is a promising strategy for what's known as precision medicine,” explain the study’s first authors, Dr. Maria Jose Silva and Dr. Lujuan Xu.
