Isothermally-Responsive Polymers Triggered by Selective Binding of Fe³⁺ to Siderophoric Catechol End-Groups

Thermoresponsive polymers have attracted huge interest as a way of developing smart/adaptable materials for biomedicine, particularly due to changes in their solubility above the LCST. However, temperature is not always an appropriate or desirable stimulus given the variety of other cellular microenvironments that exist, including pH, redox potentials, ionic strength, and metal ion concentration. Here, we achieve a highly specific, isothermal solubility switch for poly­(<i>N</i>-isopropylacrylamide) by application of ferric iron (Fe³⁺), a species implicated in a range of neurodegenerative conditions. This is achieved by the site-specific incorporation of (Fe³⁺-binding) catechol units onto the polymer chain-end, inspired by the mechanism by which bacterial siderophores sequester iron from mammalian hosts. The ability to manipulate the hydrophilicity of responsive systems without the need for a temperature gradient offers an exciting approach toward preparing increasingly selective, targeted polymeric materials

Chaxapeptin, a Lasso Peptide from Extremotolerant <i>Streptomyces leeuwenhoekii</i> Strain C58 from the Hyperarid Atacama Desert

Lasso peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that possess a unique “lariat knot” structural motif. Genome mining-targeted discovery of new natural products from microbes obtained from extreme environments has led to the identification of a gene cluster directing the biosynthesis of a new lasso peptide, designated as chaxapeptin <b>1</b>, in the genome of <i>Streptomyces leeuwenhoekii</i> strain C58 isolated from the Atacama Desert. Subsequently, <b>1</b> was isolated and characterized using high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance methods. The lasso nature of <b>1</b> was confirmed by calculating its nuclear Overhauser effect restraint-based solution structure. Chaxapeptin <b>1</b> displayed a significant inhibitory activity in a cell invasion assay with human lung cancer cell line A549