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) approximately 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.
Schmuck
Carsten
C
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany. schmuck@chemie.uni-wuerzburg.de
Rupprecht
Daniel
D
Junkers
Matthias
M
Schrader
Thomas
T
D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D019281:Dimerization; D015195:Drug Design; D005998:Glycine / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D011971:Receptors, Immunologic / Q000737:chemistry*; D018000:Receptors, Peptide / Q000737:chemistry*; D017186:Titrimetry
D009842:Oligopeptides; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor; C047981:arginyl-glycyl-aspartic acid; D005998:Glycine