Neutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics. Issue 42 (11th September 2017)

• Record Type: Journal Article
• Authors: Chirkin, Egor; Muthusamy, Viswanathan; Mann, Paul; Roemer, Terry; Nantermet, Philippe G.; Spiegel, David A.
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 42(2017)
• Page Start: 13036
• Page End: 13040
• Publication Date: 2017-09-11
• Subjects: antibodies -- antifungal agents -- cell recognition -- drug discovery -- immunology; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201707536
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : Taking aim at chitin : Design and synthesis of non‐peptidic small‐molecule immunotherapeutics for treatment of fungal infection is reported. A drug candidate was able to recruit endogenous antibodies, thus promoting the dose‐dependent phagocytosis of fungal pathogens by human immune effector cells.