Fluorescent Chemical Probes for Clinical Imaging Applications
- Dr. Marc Vendrell
- donderdag 13 oktober 2016
The Leiden Chemical Biology Lecture Committee is pleased to announce the lecture of Dr. Marc Vendrell from the University of Edinburgh on the 13th of October. Dr. Vendrell is on the frontline in the development and application of new fluorophore classes for the in vitro and in vivo imaging of biological evens; for example for imaging fungal infections in vivo and to track macrophages. This has led to many publications in top tier chemical journals as well as a recent spate of papers in journals such as the Lancet. This combination of high level organic chemistry with a strong driver toward biomedical application make him a perfect speaker in the Leiden Chemical Biology Lecture series.
Fluorescent smartprobes are chemical entities of enormous importance in chemical biology and hold outstanding potential for translation to biological and medical imaging. Our lab pioneered the derivatisation of the fluorescent 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) scaffold for multicomponent reactions (MCRs). The adaptation of MCRs to the highly fluorescent and cell permeable BODIPY scaffold provides a practical platform to develop novel compounds with unexpected features as cell imaging fluorescent probes. Using these approaches, we have developed activatable fluorophores with excellent signal-to-noise ratios, minimal fluorescence background and high selectivity for macrophages in vivo. These probes are excellent tools to non-invasively study of the mechanisms underlying macrophage function in vivo and in real time.
Our lab has also recently developed the first BODIPY-based fluorogenic amino acid and their incorporation into peptide sequences to generate highly sensitive fluorogenic probes for direct imaging of fungal pathogens. Invasive pulmonary aspergillosis (IPA) is a highly fatal disease in immunocompromised patients, and it is a frequent cause of fungal pneumonia with mortality rates up to 40%. Current diagnostic approaches for IPA rely on methods that are fraught with problems of upper airway contamination and diagnostic delays, by which time the disease may have progressed or been treated empirically with inappropriate drugs. The limitations of current diagnostic tools have prompted the development of imaging probes that can provide in situ and real-time information on the progression of infection. We have optimized the synthesis of highly fluorogenic cyclic peptide structures with bright fluorescence emission in fungal cells and high chemical stability in human bronchoalveolar lavage samples. Multi-photon imaging experiments enabled direct and straightforward visualisation of fungal pathogens in ex vivo human tissue.
Selected recent publications from the group
Bioconjugate Chem., 2016, 27, 1430.
Chem. Commun., 2016, 52, 9093.
Chem. Soc. Rev., 2016, 45, 1182.
Nat. Commun., 2016, 7, 10940.
The Lancet, 2016, 387, S17.
Bioorg. Med. Chem. Lett., 2015, 25, 4862.
J. Am. Chem. Soc., 2013, 135, 16018.