Neutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics

Systemic fungal infections represent an important public health concern, and new antifungal agents are highly desirable. Herein, we describe the design, synthesis, and biological evaluation of a novel class of antifungal compounds called antibody‐recruiting molecules targeting fungi (ARM‐Fs). Our approach relies on the use of non‐peptidic small molecules, which selectively bind fungal cells and recruit endogenous antibodies to their surfaces, resulting in immune‐mediated clearance. Using the opportunistic fungal pathogen Candida albicans as a model, we identified a highly specific bifunctional molecule able to mediate the engulfment and phagocytosis of C. albicans cells by human immune cells in biologically relevant functional assays. This work represents a novel therapeutic approach to treating fungal illness with significant potential to complement and/or combine with existing treatment strategies. Auf Chitin abzielend: Die Entwicklung und Synthese von nichtpeptidischen niedermolekularen Immuntherapeutika für die Behandlung von Pilzinfektionen wird vorgestellt. Ein Wirkstoffkandidat war in der Lage, endogene Antikörper zu rekrutieren und damit die dosisabhängige Phagozytose von Pilzpathogenen durch humane Immunaffektorzellen zu fördern.