Functionalized Prodrugs of a bacterial RNAP-Inhibitor & Bio-reversibly masked purinergic 2nd Messenger derivatives associated with Ca2+ Signaling

Abstract

This thesis aimed at conjugating two aryl-ureidothiophene carboxylic acids with moieties that provide the capacity to coordinate FeIII. In addition, spacer groups were introduced to facilitate enzymatic prodrug activation. The FeIII-coordination of the siderophore-type prodrugs was evaluated in a competitive assay to yield relative affinities. The antibiotic activity of all prodrugs, i.e. lipophilic, cationic and functionalized, was determined. In a further aspect, this thesis aimed at developing synthetic access towards AB-masked derivatives of cNMPs, (d)ADPR and NAADP. Introduction of the AB-mask in a (site-) specific way and thus in total synthesis approaches was preferably considered. Based on the complexity of the dinucleotides in molecular structure, convergent synthesis routes with a final coupling step were designed.