Ingenieurwissenschaften und zugeordnete Tätigkeiten
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ADAMTS4-specific MR-probe to assess aortic aneurysms in vivo using synthetic peptide libraries
(2022)
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.
Development of an affinity-based method for the site-selective synthesis of antibody-drug-conjugates
(2021)
For the site-selective synthesis of ADCs, a variety of obstacles must be overcome. Those include designing bifunctional affinity peptides with reasonably low 𝐾𝑑-values that couple to the mAb in a site-selective manner. These peptides should also include a functional group that links the payload to the mAb under mild conditions without adversely affecting it. The bioconjugation between peptide and antibody and the linker between peptide and payload must be stable and durable to provide safety when used for medical purposes. The usage of metals and organic solvents should be minimized. Within the project, new types of functionalized affinity peptides were designed, and their affinity towards the Fc-fragment was determined.