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Artificial Ditopic Arg‐Gly‐Asp (RGD) Receptors
Author(s) -
Schmuck Carsten,
Rupprecht Daniel,
Junkers Matthias,
Schrader Thomas
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601821
Subject(s) - intramolecular force , chemistry , titration , linker , molecular recognition , peptide , stereochemistry , covalent bond , fluorescence spectroscopy , receptor , nuclear magnetic resonance spectroscopy , molecule , arginine , binding constant , fluorescence , binding site , crystallography , amino acid , biochemistry , organic chemistry , computer science , physics , quantum mechanics , operating system
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.