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

Graphical abstract
© CRC inSight

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.

Team

Principal investigators

Project members

Publications

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.

2023

Hau J-L, Kremser H, Knogl-Tritschler S, Stefanski V, Steuber J, Fritz G. Fast IMAC purification of non-tagged S100A8/A9 (calprotectin) from Homo sapiens and Sus scrofa. Protein Expr Purif 2023;208-209: 106275. Abstract
Roll W, Faust A, Hermann S, Schafers M. Infection Imaging: Focus on New Tracers?. J Nucl Med 2023;64: 59s-67s. Abstract
Stegmann DP, Steuber J, Fritz G, Wojdyla JA, Sharpe ME. Fast fragment and compound screening pipeline at the Swiss Light Source. Methods Enzymol 2023;690: 235-284. Abstract
Steiner ST, Maisuls I, Junker A, Fritz G, Faust A, Strassert CA. Concerning the photophysics of fluorophores towards tailored bioimaging compounds: a case study involving S100A9 inflammation markers. Photochem Photobiol Sci 2023;22: 2093-2104. Abstract

2022

Honold L, Austrup M, Faust A, Konken CP, Schwegmann K, Zinnhardt B, Daniliuc CG, Haufe G, Schafers M, Kopka K, Hermann S. Towards Optimized Bioavailability of (99m)Tc-Labeled Barbiturates for Non-invasive Imaging of Matrix Metalloproteinase Activity. Mol Imaging Biol 2022;24: 434-443. Abstract

2018

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

2015

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

2014

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

2013

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

2012

Koch M, Fritz G. The structure of Ca2+-loaded S100A2 at 13-A resolution. Febs J 2012;279: 1799-1810. Abstract

2011

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

2010

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

2007

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