Cover Feature: Bioinspired Design of Lysolytic Triterpenoid–Peptide Conjugates that Kill African Trypanosomes (ChemBioChem 10/2019)

Bioinspired drug discovery. A lysolytic triterpenoid–peptide conjugate was been developed in a stepwise fashion as a synthetic reagent to interfere with the growth of African trypanosomes, the causative agent of African sleeping sickness. Synthesis of the antiparasitic conjugate is based on the design principles of naturally existing trypanolytic factors, that is, it follows a bioinspired drug discovery strategy, as symbolized by the bamboo plant on the left. The spiral bamboo branch and the Fibonacci spiral in the background emphasize the reliance of the trypanocidal properties of the peptide on pH‐dependent conversion from a random conformation to an amphiphilic helix. As designed, the triterpenoid–peptide kills African trypanosomes in a dose‐dependent manner through lysosomal lysis; this demonstrates a proof‐of‐principle for the forward‐design or re‐engineering of novel therapeutic reagents especially for neglected tropical diseases. More information can be found in the communication by H. U. Göringer et al. on page 1251 in Issue 10, 2019 (DOI: 10.1002/cbic.201800674).