A rationally designed oligopeptide shows significant conformational changes upon binding to sulphate ions

Oligopeptides that interact with oxoanions were developed by rational desig n methods. The substrate-binding site of the enzyme purine nucleoside phosp horylase served as a model for the design of the ionophores. The amino acid s involved in the complexation of oxoanions were linked through flexible sp acer residues. These spacers were chosen such that the relative orientation of the interacting amino acids was conserved. Several peptide sequences we re preselected based on intermolecular H-bond frequencies, These frequencie s were calculated from molecular dynamics trajectories of the corresponding peptide-anion complexes and used to score the binding properties of the pe ptides. The most promising peptides were prepared using solid phase peptide synthesis. Anion binding of the peptide ionophores was screened using circ ular dichroism (CD) and confirmed by NMR spectroscopy. CD measurements perf ormed in methanol revealed a significant conformational change of a linear undecapeptide upon binding to sulphate ions. Two-dimensional-NMR experiment s confirmed that a conformation with high helical content is formed in the presence of sulphate ions. These conformational changes induced by the anio n stimulate the development of new transduction mechanisms in chemical sens ors. (C) 2001 Elsevier Science B.V. All rights reserved.