We are pleased to announce the publication of the paper ‘Functionalized in Triplicate: A Ring-By-Ring Approach to Tailored Prodiginine Derivatives for Site-Specific Conjugation Through Click Chemistry’ by T. Moritz Weber.

Prodigiosin and related prodiginins are structurally diverse natural compounds produced by bacteria with remarkable biological activities, including antimicrobial, antitumour and immunosuppressive properties. Although their unique structure allows passive diffusion through membranes, it is often accompanied by low target specificity, which hinders their use as targeted therapeutics.

The current work presents a new chemical methodology that allows prodiginins to be modified in such a way that click chemistry reactions are possible at all three pyrrole rings. By incorporating azides and maleimides into rings A, B and C, prodiginine-based conjugates with proteins can be produced for the first time using azide-alkyne cycloadditions (CuAAC and SPAAC) and thiol-maleimide additions.

The synthesis routes developed comprise 12–15 steps with total yields of 3.2–4.7% and provide valuable building blocks for extending the repertoire of click chemistry to other natural products containing pyrrole, pyrrolidinone and tetramine acids. This opens up new perspectives for the development of targeted alkaloid therapeutics.

We congratulate Moritz on this exciting publication!

The publication is available online.