Effects of sequence context on the binding of tryptophan-containing peptides by the cucurbit[8]uril–methyl viologen complex

Abstract

This paper describes a novel assay for measuring the relative extent of peptide binding in a large parallel format and the use of this assay to explore the effects of sequence context on the binding of tryptophan (Trp)-containing peptides by the synthetic receptor comprising the noncovalent complex between cucurbit[8]uril and methyl viologen (i.e. Q8√MV). The extent of quenching of Trp fluorescence upon binding to Q8√MV was used to measure the relative extent of binding and thus the relative affinities of 104 Trp-containing peptides, in parallel, using a fluorescence plate reader. This study resulted in the remarkable observation that the identity of the amino acid residues at positions adjacent to the Trp-binding site has little if any influence on the binding affinity. This finding suggests that Q8√MV should be effective for the recognition of Trp residues within a broad range of peptide sequences.

Keywords::

• cucurbit[8]uril
• viologen
• tryptophan
• peptide
• assay

Acknowledgements

Financial support from the National Science Foundation (CHE-0748483), the Welch Foundation (W-1640), the Henry Dreyfus Teacher-Scholar Awards Programme and Trinity University is gratefully acknowledged. Omar Ali was a Beckman Scholar.

Supplementary Information

Mass spectra and HPLC traces of peptides from the library.