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. 2019 Apr 9;10:644. doi: 10.3389/fimmu.2019.00644

Figure 1.

Figure 1

Design of immunogenic bifunctional compounds for enhancing neutrophil activity against fungi. (A) Diagram shows conceptual basis of bifunctional compounds design to stimulate interactions between specific immune cell types and microbes. The bifunctional compounds used in this study utilize antifungal TMs and a formyl peptide EM with the aim of stimulating neutrophil activity against fungi. (B) Chemical structures detailing synthesis of C-001/C-014 and C-016 by fusion of an fMLP EM with caspofungin (CAS) and amphotericin B (AmB) TM, respectively. Detailed synthesis methods can be found in the Supplementary Material. (C) Hypothesized mode of action: Binding of formyl peptides enhances neutrophil activation, while molecules decorating the fungal surface further stimulate their anti-microbial activities. (D) Targeting of compounds to the fungal surface via the antifungal TM caspofungin. Following 30 min of treatment with caspofungin-BODIPY conjugate, RFP-expressing hyphal structures are clearly labeled with the fluorescent signal from BODIPY (ii). This specific decoration of the fungal surface does not occur using a BODIPY-conjugated formyl peptide control (i). Scale as shown.