Vielfalt ist für Chemiker wie Professor John Moses vom Cold Spring Harbor Laboratory (CSHL) ein wesentlicher Weg zur Entdeckung. Je breiter das Spektrum der untersuchten Moleküle ist, desto höher sind die Chancen, etwas Wertvolles zu identifizieren. Die jüngsten Fortschritte im Labor von Moses ermöglichen es ihnen, schnell eine große Vielfalt komplexer Moleküle zu konstruieren. Moses hofft, dass es unter diesen Molekülen neue und wirksame Krebsbehandlungen geben wird.
Zusammen mit K. Barry Sharpless, einem zweifachen Nobelpreisträger, hat Moses‘ Labor eine chemische Umwandlung namens Phosphorfluoridaustausch (PFEx) entwickelt. PFEx fügt chemische Bausteine effizient zusammen, um neue Moleküle zu bilden, in einem zuverlässigen Prozess, der als Klick-Chemie bekannt ist. Die Click-Chemie bietet Chemikern bereits ein leistungsstarkes Werkzeugset. Als neueste Ergänzung zu diesem Werkzeugkasten orientiert sich PFEx an der Biologie und nutzt Phosphor als chemischen Verbinder.
Im Inneren der Zellen sorgt Phosphor für die Struktur[{” attribute=””>DNA and holds together essential energy-storing molecules. It’s a versatile connector. It can readily connect multiple chemical groups. These groups can be arranged around the phosphorous hub to create three-dimensional shapes.
Moses says: “Nature has recognized its importance—it’s a privileged group. If we’re trying to make drugs that interact with biology, we should not ignore that fact.”
Chemists can now use PFEx to click together multiple different chemical components around a single phosphorous hub. By incorporating more phosphorous connectors, they can build even more complex molecules. “We’re now decorating this three-dimensional linkage. And that’s going to allow us to access some new chemical space,” says CSHL Research Investigator Joshua Homer. “When you access new space, you’re accessing new function.”
PFEx reactions might even enable drugs to latch onto their targets inside the body. Moses’ team has already begun exploring PFEx as a source of cancer therapeutics. One benefit to this approach is that researchers can optimize the reactivity of the molecules involved in PFEx reactions. This could ensure potential drugs interact only with their desired targets, reducing the risk of side effects.
The researchers expect their new kind of click chemistry will help create materials with useful properties. For example, PFEx might be used to incorporate flame retardants or antimicrobials into new surfaces. Moses says PFEx materials will have an important advantage over the “forever chemicals” found in many of today’s products. Phosphorous bonds are not excessively stable. This means they can be easily broken down when a product is ready for recycling.
Reference: “Phosphorus fluoride exchange: Multidimensional catalytic click chemistry from phosphorus connective hubs” by Shoujun Sun, Joshua A. Homer, Christopher J. Smedley, Qing-Qing Cheng, K. Barry Sharpless and John E. Moses, 7 June 2023, Chem.
DOI: 10.1016/j.chempr.2023.05.013
The study was funded by the National Cancer Institute, Cold Spring Harbor Laboratory, Northwell Health, the F. M. Kirby Foundation, the Sunshine Foundation, S. J. Edwards, the Starr Foundation, The Wasily Family Foundation, La Trobe University, and the National Institutes of Health.