Role of a two-residue spacer in an α,β-didehydrophenylalanine containing hexapeptide:: Crystal and solution structure of Boc-Val-ΔPhe-Leu-Ala-ΔPhe-Ala-OMe

The peptide Boc-Val(1)-DeltaPhe(2)-Leu(3)-Ala(4)-DeltaPhe(5)-Ala(6)-OMc has been examined for the structural consequence of placing a two-residue segment between the APhe residues. The peptide is stabilized by four consecutive beta-turns. The overall conformation of the molecule is a right-handed 3(10)-helix. with average (Phi, psi) values (-67.7degrees -22.7degrees), unwound at the C-terminus. The H-1 NMR results also suggest that the peptide maintains its 3(10)-helical structure in solution as observed in the crystal state, The crystal structure is stabilized through head-to-tail hydrogen bonds and a repertoire of aromatic interactions laterally directed between adjacent helices, which are antiparallel to each other, The aromatic ring of forms the hub of multicentred interactions, namely as a donor in aromatic C-H(...)pi and aromatic C-(HO)-O-...=C interactions and as an acceptor in a CH(3)(...)pi interaction, The present structure uniquely illustrates the unusual capability of a DeltaPhe ring to host such concerted interactions and suggests its exploitation in Introducing long-range interactions in the folding of supersecondary structures. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.