Artificial ditopic arg-gly-asp (RGD) receptors
2007
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 Ka≈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 (Ka=5000 m−1). The recognition events have been studied with NMR spectroscopy, UV/Vis spectroscopy, and fluorescence titrations.
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