Artificial Ditopic Arg‐Gly‐Asp (RGD) Receptors

Covalent fusion of two artificial recognition motifs for arginine and aspartate resulted in a new class of ditopic RGD receptor molecules, 1 – 4 . The two binding sites for the oppositely charged amino acid residues are linked by either flexible linkers of different length (in 1 – 3 ) or a rigid aromatic spacer (in 4 ). These spacers are shown to be critical for the complexation efficiency of the artificial hosts. If the linkers are too flexible, as in 1 – 3 , an undesired intramolecular self‐association occurs within the host and competes with, and thereby weakens, substrate binding. The rigid aromatic linker in 4 prevents any intramolecular self‐association and hence efficient RGD binding is observed, even in buffered water (association constant of K a ≈3000  m −1 ). A further increase in hydrophobic contacts, as in host 16 , can complement the specific Coulomb attractions, thereby leading to an even more stable complex ( K a =5000  m −1 ). The recognition events have been studied with NMR spectroscopy, UV/Vis spectroscopy, and fluorescence titrations.