Termhedron Lemn. Vol. 35. No. 35. pp. 6413-6416. 1994 Elrvicr Science zyxwvutsrqpon Ltd Printed in Grea Britain oo404039/94 57.ooto.00 0040-4039(94)01369-1 Peptide Complexatjon in Water. Sequence-SelectiveBinding with Simple Dye Molecules. Helma Wennemers and W. Clark Still Department of Chemistry, Columbia University, New York, NY 10027 Abstract Many commercially available dyes bind certain acylated tripeptides with high selectivity on hydrophilic poly(ethylene glycol)-polystyrene beads in water. One of the most common methods for assessing substrate/receptor binding entails labeling a substrate or receptor with a colored or fluorescent dye. Such labeling is used in a number of important biological marking techniques including immunofluorescence and fluorescence-based zyxwvutsrqponml in situ hybridization. It has recently zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA been used to probe the binding of small biological molecules to synthetic receptors.1 Whatever the system, binding studies using labeled material assume that the presence of label does not significantly alter receptor-substrate binding. In fact, we find that many common dyes associate wtth peptides in water with substantial selectivity for their amino acid composition or sequence. Our results indicate that dyes in binding assays need to be chosen with great care to avoid label-induced artifacts. They also suggest novel structural motifs that may be used as the b a sis o f ne w se q ue nc e - se le c tive re c e pto rs for peptides.