ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries

Jan O. Kaufmann, Julia Brangsch, Avan Kader, Jessica Saatz, Dilyana B. Mangarova, Martin Zacharias, Wolfgang E. Kempf, Timm Schwaar, Marco Ponader, Lisa C. Adams, Jana Möckel, Rene M. Botnar, Matthias Taupitz, Lars Mägdefessel, Heike Traub, Bernd Hamm, Michael G. Weller and Marcus R. Makowski ()
Additional contact information
Jan O. Kaufmann: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Julia Brangsch: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Avan Kader: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Jessica Saatz: Division 1.1 Inorganic Trace Analysis
Dilyana B. Mangarova: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Martin Zacharias: Technische Universität München (TUM)
Wolfgang E. Kempf: Technische Universität München (TUM)
Timm Schwaar: Division 1.0 SAFIA Technologies
Marco Ponader: Division 1.5 Protein Analysis
Lisa C. Adams: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Jana Möckel: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Rene M. Botnar: School of Biomedical Engineering and Imaging Sciences
Matthias Taupitz: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Lars Mägdefessel: Technische Universität München (TUM)
Heike Traub: Division 1.1 Inorganic Trace Analysis
Bernd Hamm: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Michael G. Weller: Division 1.5 Protein Analysis
Marcus R. Makowski: Humboldt-Universität zu Berlin, and Berlin Institute of Health

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract The incidence of abdominal aortic aneurysms (AAAs) has substantially increased during the last 20 years and their rupture remains the third most common cause of sudden death in the cardiovascular field after myocardial infarction and stroke. The only established clinical parameter to assess AAAs is based on the aneurysm size. Novel biomarkers are needed to improve the assessment of the risk of rupture. ADAMTS4 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 4) is a strongly upregulated proteoglycan cleaving enzyme in the unstable course of AAAs. In the screening of a one-bead-one-compound library against ADAMTS4, a low-molecular-weight cyclic peptide is discovered with favorable properties for in vivo molecular magnetic resonance imaging applications. After identification and characterization, it’s potential is evaluated in an AAA mouse model. The ADAMTS4-specific probe enables the in vivo imaging-based prediction of aneurysm expansion and rupture.

Date: 2022
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DOI: 10.1038/s41467-022-30464-8

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