The interactions and conformational changes that lead to the conversion of the normal prion protein (PrPc) to its pathogenic form, PrPsc, are still being elucidated. Using Surface Plasma Resonance (SPR), we provide evidence that a synthetic peptide (PrP144-167) corresponding to residues comprising the a helix 1-beta strand 2 domain of PrPc is able to interact and bind to immobilised recombinant human PrP (rHuPrP) in a dose-dependent manner. The interaction is pH dependent with an increase in binding observed as the pH is lowered, particularly between pH 6.5 and pH 5.5 suggesting a specific role for His(155) in the interaction, confirmed by covalent modification of this residue in the peptide with diethylpyrocarbonate (DEPC). Circular dichroism analysis of PrP144-167 revealed no secondary structure motifs across the pH range investigated. Possible pH related structural changes of immobilised rHuPrP are also discussed with regard to the increased affinity for PrP144-167. (c) 2007 Elsevier Inc. All rights reserved.