Structure-Activity Relationships of Triple-Action Platinum(IV) Prodrugs with Albumin-Binding Properties and Immunomodulating Ligands

Chemotherapy with platinum complexes is essential for clinical anticancer therapy. However, due to side effects and drug resistance, further drug improvement is urgently needed. Herein, we report on triple-action platinum­(IV) prodrugs, which, in addition to tumor targeting via maleimide-mediated albumin binding, release the immunomodulatory ligand 1-methyl-d-tryptophan (1-MDT). Unexpectedly, structure–activity relationship analysis showed that the mode of 1-MDT conjugation distinctly impacts the reducibility and thus activation of the prodrugs. This in turn affected ligand release, pharmacokinetic properties, efficiency of immunomodulation, and the anticancer activity in vitro and in a mouse model in vivo. Moreover, we could demonstrate that the design of albumin-targeted multi-modal prodrugs using platinum­(IV) is a promising strategy to enhance the cellular uptake of bioactive ligands with low cell permeability (1-MDT) and to improve their selective delivery into the malignant tissue. This will allow tumor-specific anticancer therapy supported by a favorably tuned immune microenvironment

Eteokles in Spain? On Brecht’s Mein Bruder war ein Flieger

One of Bertolt Brecht’s most famous poems, Mein Bruder war ein Flieger, is often invoked as a manifesto for pacifist ideals, but some essential questions (who is the lyric I? what is the literal meaning of the poem?) have hardly received any attention. By evoking the poem’s nature as a Kinderlied, the context of its first publication, and its relationship with Brecht’s play Die Gewehre der Frau Carrar, this article tentatively identifies the source of its final pointe in a famous passage of Aeschylus’ Seven against Thebes, thereby suggesting—on the basis of textual comparisons—an example of far-reaching, ideological Antikerezeption in Brecht’s oeuvre, working all the way down to his Kalendergeschichten and to his Antigone