Membrane interaction
constitutes to be an essential parameter in
the mode of action of entities such as proteins, as well as cell-penetrating
and antimicrobial peptides, resulting in noninvasive or lytic activities
depending on the membrane compositions and interactions. Recently,
a nanobody able to interact with the top priority, multidrug-resistant
bacterial pathogen Acinetobacter baumannii was discovered, although binding took place with fixed cells only.
To potentially overcome this limitation, linear peptides corresponding
to the complementarity-determining regions (CDR) were synthesized
and fluorescently labeled. Microscopy data indicated clear membrane
interactions of the CDR3 sequence with living A. baumannii cells, indicating both the importance of the CDR3 as part of the
parent nanobody paratope and the improved binding ability and thus
avoiding the need for permeabilization of the cells. In addition,
cyclization of the peptide with an additionally introduced rigidifying
1,2,3-triazole bridge retains its binding ability while proteolytically
protecting the peptide. Overall, this study resulted in the discovery
of novel peptides binding a multidrug-resistant pathogen.