Search

The rational design and synthesis of a Trp-BODIPY cyclic peptide for the fluorescent labelling of apoptotic bodies is described. Affinity assays, confocal microscopy and flow cytometry analysis confirmed the binding of the peptide to negatively-charged phospholipids associated with apoptosis, and its applicability for the detection and characterisation of subcellular structures released by apoptotic cells.

The G protein‐coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited fluorescent probes or antibodies for direct imaging of these receptors in cells and intact tissues, which can help to interrogate their multiple biological roles. Herein, we describe the rational design and characterization of a new acid‐resistant BODIPY‐based amino acid (Trp‐BODIPY PLUS), and its implementation for solid‐phase synthesis of fluorescent bioactive peptides. Trp‐BODIPY PLUS retains the binding capabilities of both short linear and cyclic peptides and displays notable turn‐on fluorescence emission upon target binding for wash‐free imaging. Finally, we employed Trp‐BODIPY PLUS to prepare some of the first fluorogenic kisspeptin‐based probes and visualized the expression and localization of GPR54 receptors in human cells and in whole mouse pancreatic islets by fluorescence imaging. [ABSTRACT FROM AUTHOR]

Cytotoxic immune cells, including T lymphocytes (CTLs) and natural killer (NK) cells, are essential components of the host response against tumors. CTLs and NK cells secrete granzyme A (GzmA) upon recognition of cancer cells; however, there are very few tools that can detect physiological levels of active GzmA with high spatiotemporal resolution. Herein, we report the rational design of the near‐infrared fluorogenic substrates for human GzmA and mouse GzmA. These activity‐based probes display very high catalytic efficiency and selectivity over other granzymes, as shown in tissue lysates from wild‐type and GzmA knock‐out mice. Furthermore, we demonstrate that the probes can image how adaptive immune cells respond to antigen‐driven recognition of cancer cells in real time. [ABSTRACT FROM AUTHOR]

The multiple applications of super‐resolution microscopy have prompted the need for minimally invasive labeling strategies for peptide‐guided fluorescence imaging. Many fluorescent reporters display limitations (e.g. large and charged scaffolds, non‐specific binding) as building blocks for the construction of fluorogenic peptides. Herein we have built a library of benzodiazole amino acids and systematically examined them as reporters for background‐free fluorescence microscopy. We have identified amine‐derivatized benzoselenadiazoles as scalable and photostable amino acids for the straightforward solid‐phase synthesis of fluorescent peptides. Benzodiazole amino acids retain the binding capabilities of bioactive peptides and display excellent signal‐to‐background ratios. Furthermore, we have demonstrated their application in peptide‐PAINT imaging of postsynaptic density protein‐95 nanoclusters in the synaptosomes from mouse brain tissues. [ABSTRACT FROM AUTHOR]

Fungal infections caused by Candida species are among the most prevalent in hospitalized patients. However, current methods for the detection of Candida fungal cells in clinical samples rely on time‐consuming assays that hamper rapid and reliable diagnosis. Herein, we describe the rational development of new Phe‐BODIPY amino acids as small fluorogenic building blocks and their application to generate fluorescent antimicrobial peptides for rapid labelling of Candida cells in urine. We have used computational methods to analyse the fluorogenic behaviour of BODIPY‐substituted aromatic amino acids and performed bioactivity and confocal microscopy experiments in different strains to confirm the utility and versatility of peptides incorporating Phe‐BODIPYs. Finally, we have designed a simple and sensitive fluorescence‐based assay for the detection of Candida albicans in human urine samples. [ABSTRACT FROM AUTHOR]

Fluorescent cyclic peptides are excellent chemical scaffolds to build optical agents for molecular imaging. In addition to their favorable physicochemical properties, they can be modified with multiple organic fluorophores and generate useful probes for biological assays targeting specific proteins, namely receptors or enzymes. In this article, we review recent advances in the synthetic approaches for the preparation of fluorescent cyclic peptides as well as some of their applications in biological imaging, from in vitro live‐cell imaging studies to in vivo characterization of preclinical models. [ABSTRACT FROM AUTHOR]