title: Spacer-free BODIPY fluorogens in antimicrobial peptides for direct imaging of fungal infection in human tissue.
abstract: Fluorescent antimicrobial peptides are promising structures for in situ, real-time imaging of fungal infection. Here we report a fluorogenic probe to image Aspergillus fumigatus directly in human pulmonary tissue. We have developed a fluorogenic Trp-BODIPY amino acid with a spacer-free C-C linkage between Trp and a BODIPY fluorogen, which shows remarkable fluorescence enhancement in hydrophobic microenvironments. The incorporation of our fluorogenic amino acid in short antimicrobial peptides does not impair their selectivity for fungal cells, and enables rapid and direct fungal imaging without any washing steps. We have optimized the stability of our probes in human samples to perform multi-photon imaging of A. fumigatus in ex vivo human tissue. The incorporation of our unique BODIPY fluorogen in biologically relevant peptides will accelerate the development of novel imaging probes with high sensitivity and specificity.
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, Barcelona 08028, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Mendive-Tapia
authors.affiliation: Manchester Fungal Infection Group, Institute of Inflammation and Repair, University of Manchester, CTF Building, Grafton St, Manchester M13 9NT, UK.
authors.forename: Can
authors.initials: C
authors.lastname: Zhao
authors.affiliation: MRC/UoE Centre for Inflammation Research, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Ahsan R
authors.initials: AR
authors.lastname: Akram
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, Barcelona 08028, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Preciado
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, Barcelona 08028, Spain.|Department Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, Barcelona 08028, Spain.|CIBER-BBN, Networking Centre for Bioengineering, Biomaterials and Nanomedicine, Baldiri Reixac 10-12, Barcelona 08028, Spain.|School of Chemistry, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: Edinburgh Cancer Research Centre, University of Edinburgh, Crewe South Road, Edinburgh EH4 2XR, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Lee
authors.affiliation: Edinburgh Cancer Research Centre, University of Edinburgh, Crewe South Road, Edinburgh EH4 2XR, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Serrels
authors.affiliation: Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona Science Park, Baldiri Reixac 10-12, Barcelona 08028, Spain.
authors.forename: Nicola
authors.initials: N
authors.lastname: Kielland
authors.affiliation: Manchester Fungal Infection Group, Institute of Inflammation and Repair, University of Manchester, CTF Building, Grafton St, Manchester M13 9NT, UK.
authors.forename: Nick D
authors.initials: ND
authors.lastname: Read
authors.affiliation: CIBER-BBN, Networking Centre for Bioengineering, Biomaterials and Nanomedicine, Baldiri Reixac 10-12, Barcelona 08028, Spain.|Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona Science Park, Baldiri Reixac 10-12, Barcelona 08028, Spain.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Lavilla
authors.affiliation: MRC/UoE Centre for Inflammation Research, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Vendrell
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D001228:Aspergillosis / Q000175:diagnosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D001896:Boron Compounds / Q000737:chemistry*; D003952:Diagnostic Imaging / Q000295:instrumentation* / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008168:Lung / Q000382:microbiology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000935:Antifungal Agents; D001896:Boron Compounds; D005456:Fluorescent Dyes; D010455:Peptides