END-GROUP MODIFIED RETRO-INVERSO ISOMERS OF TRIPEPTIDE OXYTOCIN ANALOGS - BINDING TO NEUROPHYSIN-II AND ENHANCEMENT OF ITS SELF-ASSOCIATIONPROPERTIES

The importance of peptide backbone structure in peptide/protein recogn ition events has been tested evaluating the binding properties of end- group modified retro-inverso isomers of MYF and LYF amides, tripeptide s able to mimic oxytocin in binding neurophysin II and in potentiating its self-association. The isomers, topochemically related to their pa rent peptides, have been prepared respectively from all-D N-acetyl-FYM and N-acetyl-FYL amides via the Hofmann-type rearrangement mediated b y iodobenzene bis-trifluoroacetate. Retro-inverso isomers recognised n europhysin II with similar affinity as the parent peptides, as determi ned by analytical affinity chromatography on columns prepared immobili sing neurophysin II on preactivated supports. In addition, their effec t on neurophysin II self-association was similar to the tripeptide oxy tocin analogues, potentiating neurophysin II dimerization to the same extent, as evaluated by solid-phase binding assays on microtiter plate s coated with neurophysin II. Recognition specificity of retro-inverso isomers was further demonstrated by their inhibitory effect on the in teraction between neurophysin II and oxytocin tripeptide analogues. Re sults suggest that only the proper orientation of the alpha-amino grou p and of the side chains plays a dominant role in the binding of tripe ptide analogues to neurophysin II and potentiation of its self-associa tion, while the peptide backbone topology has little influence on the recognition process. (C) Munksgaard 1995.