End-group modified retro-inverso isomers of tripeptide oxytocin analogues: binding to neurophysin II and enhancement of its self-association properties.

The importance of peptide backbone structure in peptide/protein recognition events has been tested evaluating the binding properties of end-group modified retro-inverso isomers of MYF and LYF amides, tripeptides able to mimic oxytocin in binding neurophysin II and in potentiating its self-association. The isomers, topochemically related to their parent peptides, have been prepared respectively from all-D N-acetyl-FYM and N-acetyl-FYL amides via the Hofmann-type rearrangement mediated by iodobenzene bis-trifluoroacetate. Retro-inverso isomers recognised neurophysin II with similar affinity as the parent peptides, as determined by analytical affinity chromatography on columns prepared immobilising neurophysin II on preactivated supports. In addition, their effect on neurophysin II self-association was similar to the tripeptide oxytocin analogues, potentiating neurophysin II dimerization to the same extent, as evaluated by solid-phase binding assays on microtiter plates coated with neurophysin II. Recognition specificity of retro-inverso isomers was further demonstrated by their inhibitory effect on the interaction between neurophysin II and oxytocin tripeptide analogues. Results suggest that only the proper orientation of the alpha-amino group and of the side chains plays a dominant role in the binding of tripeptide analogues to neurophysin II and potentiation of its self-association, while the peptide backbone topology has little influence on the recognition process.