Targeting of S100A8/A9 for imaging of inflammatory disorders
Principal investigators: Andreas Faust, Günter Fritz
Project number: CRC 1450 A03
Project term: 01/2021–12/2024
Activated monocytes and granulocytes are key to inflammatory diseases and release the alarmin S100A8/A9 in high concentrations, promoting sterile as well as infectious inflammatory processes via TLR4 (1). We will establish a specific S100A8/A9 small molecule ligand through combination of X-ray structure analysis and chemical synthesis (2, 3). The ligand will be linked to different labels suited for PET, SPECT, fluorescent or photoacoustic imaging techniques (4).
In summary, we will create a new S100 alarmin-based imaging toolset to monitor inflammatory responses with respect to their spatial location and temporal dynamics at various scales in living organisms.
The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.
Voeller T, Faust A, Roth J, Schafers M, Vogl T, Hermann S. A Non-Peptidic S100A9 Specific Ligand for Optical Imaging of Phagocyte Activity In Vivo. Mol Imaging Biol 2018;20: 407-416. Abstract
Faust A, Voller T, Busch F, Schafers M, Roth J, Hermann S, Vogl T. Development and evaluation of a non-peptidic ligand for the molecular imaging of inflammatory processes using S100A9 (MRP14) as a novel target. Chem Commun (Camb) 2015;51: 15637-15640. Abstract
Vogl T, Eisenblatter M, Voller T, Zenker S, Hermann S, van Lent P, Faust A, Geyer C, Petersen B, Roebrock K, Schafers M, Bremer C, Roth J. Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity. Nat Commun 2014;5: 4593. Abstract
Damo SM, Kehl-Fie TE, Sugitani N, Holt ME, Rathi S, Murphy WJ, Zhang Y, Betz C, Hench L, Fritz G, Skaar EP, Chazin WJ. Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens. Proc Natl Acad Sci U S A 2013;110: 3841-3846. Abstract
Fritz G. X-ray structural analysis of S100 proteins. Methods Mol Biol 2013;963: 87-97. Abstract
Koch M, Fritz G. The structure of Ca2+-loaded S100A2 at 13-A resolution. Febs J 2012;279: 1799-1810. Abstract
Baumann A, Faust A, Law MP, Kuhlmann MT, Kopka K, Schäfers M, Karst U. Metabolite identification of a radiotracer by electrochemistry coupled to liquid chromatography with mass spectrometric and radioactivity detection. Anal Chem 2011;83: 5415-5421. Abstract
Ostendorp T, Diez J, Heizmann CW, Fritz G. The crystal structures of human S100B in the zinc- and calcium-loaded state at three pH values reveal zinc ligand swapping. Biochim Biophys Acta 2011;1813: 1083-1091. Abstract
Breyholz HJ, Wagner S, Faust A, Riemann B, Höltke C, Hermann S, Schober O, Schäfers M, Kopka K. Radiofluorinated pyrimidine-2,4,6-triones as molecular probes for noninvasive MMP-targeted imaging. ChemMedChem 2010;5: 777-789. Abstract
Ostendorp T, Leclerc E, Galichet A, Koch M, Demling N, Weigle B, Heizmann CW, Kroneck PMH, Fritz G. Structural and functional insights into RAGE activation by multimeric S100B. Embo J 2007;26: 3868-3878. Abstract