Analysis of lanthanide-binding peptides in the gas phase by advances mass spectrometry methods saves sample amount and time.

Selective peptide ligands for lanthanides (Ln) have multiple applications in, for example, Ln-separation and recycling or as lanthanide-binding tags. Optimizing peptides for Ln-binding can be cumbersome and many techniques need high sample volumes. Here short 12-aminoacid peptides are investigated based on the metal-binding loops of the natural Ln-binding protein lanmodulin with advanced gas-phase techniques such as ion mobility spectrometry, collision-induced dissociation, and electrospray ionization to gain insight into binding residues and possible differences between sequences. Both the natural sequences as well as peptides that are synthesized in “reverse” order are investigated and it is found that the trends observed in solution measurements are well reproduced by gas-phase measurements.