Short talk:
Catch Me if You Can - Entrapment of Methylated Arginine by Supramolecular Hosts

Bianca Emma Kamba1, Zoey Warmerdam2, My-Hue Le3, Thomas Schrader3, Lyle Isaacs4, Fraser Hof2, Peter Bayer1

1University of Duisburg-Essen, Institute of Biology and Center for Medical Biotechnology, Essen, Germany,
2University of Victoria, Institute of Chemistry, Victoria, Canada,
3University of Duisburg- Essen, Institute of Organic Chemistry, Essen, Germany,
4University of Maryland, Institute of Chemistry and Biochemistry, College Park, United States

The World Health Organization estimated that 1.28 billion adults aged 30-79 years worldwide suffer from hypertension (2021). Patients with elevated blood pressure develop more cardiovascular complications. Therefore, cardiovascular diseases are major cause of premature death. Nitric oxide (NO), produced by the endothelial isoform of NO synthase (eNOS) in the vascular endothelium, plays a key role in the regulation of blood pressure. Patients with hypertension, hypercholesterolemia, diabetes, and chronic kidney failure show an elevated level of asymmetric dimethylarginine (ADMA), which acts as an endogenous competitive inhibitor of eNOS. The aim of our study is to introduce a supramolecular host to entrap ADMA and thus prevent the inhibition of eNOS.

First, we tested three different classes of supramolecular hosts to identify the best ADMA binder [1]. We are currently establishing an in vitro and two in vivo assays to quantify host binding to ADMA and their effect on the eNOS activity. We already expressed and purified recombinant eNOS for the in vitro inhibition assay. In addition, two in vivo models are investigated: (a) human umbilical vein endothelial cells (HUVEC), which are able to express eNOS and thus produce NO themselves, and (b) we will be establishing an inducible expression HEK cell line system for external control and regulation of eNOS expression.

[1] Warmerdam and Kamba et al. 2022, ChemBioChem 23, e202100502

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