Recognition of solvent exposed protein surfaces using anthracene derived receptors.
A new class of receptor is described that can selectively bind to the solvent exposed surface of proteins such as cytochrome c and lysozyme with low micromolar affinity over cytochrome c551, alpha-lactalbumin, myoglobin and RNase A, under physiologically relevant conditions (5 mM phosphate, pH 7.4). The use of anthracene as a hydrophobic scaffold allows the receptor to act as a selective chemosensor via fluorescence quenching or FRET. The study reveals that co-operative electrostatic interactions over a large surface area dominate binding. Further investigations reveal that the receptor binds to the solvent exposed heme edge of cytochrome c inhibiting its reaction with small reducing agents and validating the strategy for the disruption of protein function.
Wilson
Andrew J
AJ
Department of Chemistry, PO Box 208107, 225 Prospect Street, Yale University, New Haven, CT 06520-8107, USA.
Hong
Jason
J
Fletcher
Steven
S
Hamilton
Andrew D
AD
D000818:Animals; D000873:Anthracenes / Q000737:chemistry*; D002417:Cattle; D045304:Cytochromes c / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D006736:Horses; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D055672:Static Electricity
D000873:Anthracenes; D011506:Proteins; D012997:Solvents; D045304:Cytochromes c; D012259:Ribonuclease, Pancreatic