Lysine and arginine play a key role in numerous biol. recognition processes controlling, inter alia, gene regulation, glycoprotein targeting and vesicle transport. They are also found in signaling peptide sequences responsible, e.g., for bacterial cell wall biosynthesis, Alzheimer peptide aggregation and skin regeneration. Almost none of all artificial receptor structures reported to date are selective and efficient for lysine residues in peptides or proteins. An artificial mol. tweezer is introduced which displays an exceptionally high affinity for lysine (Ka ~ 5000 in neutral phosphate buffer). It features an electron-rich torus-shaped cavity adorned with two peripheral anionic phosphonate groups. Exquisite selectivity for arginine and lysine is achieved by threading the whole amino acid side chain through the cavity and subsequent locking by formation of a phosphonate-ammonium/guanidinium salt bridge. This pseudorotaxane-like geometry is also formed in small basic signaling peptides, which can be bound with unprecedented affinity in buffered aq. soln. NMR titrns., NOESY and VT expts. as well as ITC measurements and Monte Carlo simulations unanimously point to an enthalpy-driven process utilizing a combination of van der Waals interactions and substantial electrostatic contributions for a conformational lock. Since DMSO and acetonitrile compete with the amino acid guest inside the cavity, a simple change in the cosolvent compn. renders the whole complexation process reversible.