β ‐Peptidic Secondary Structures Fortified and Enforced by Zn 2+ Complexation – On the Way to β ‐Peptidic Zinc Fingers?

The correlation between β 2 ‐, β 3 ‐, and β 2,3 ‐amino acid‐residue configuration and stability of helix and hairpin‐turn secondary structures of peptides consisting of homologated proteinogenic amino acids is analyzed ( Figs. 1–3 ). To test the power of Zn 2+ ions in fortifying and/or enforcing secondary structures of β ‐peptides, a β ‐decapeptide, 1 , four β ‐octapeptides, 2 – 5 , and a β ‐hexadecapeptide, 10 , have been devised and synthesized. The design was such that the peptides would a ) fold to a 14‐ helix ( 1 and 3 ) or a hairpin turn ( 2 and 4 ), or form neither of these two secondary structures ( i.e. , 5 ), and b ) carry the side chains of cysteine and histidine in positions, which will allow Zn 2+ ions to use their extraordinary affinity for RS − and the imidazole N‐atoms for stabilizing or destabilizing the intrinsic secondary structures of the peptides. The β ‐hexadecapeptide 10 was designed to a ) fold to a turn, to which a 14‐ helical structure is attached through a β ‐dipeptide spacer, and b ) contain two cysteine and two histidine side chains for Zn complexation, in order to possibly mimic a Zn‐finger motif. While CD spectra ( Figs. 6–8 and 17 ) and ESI mass spectra ( Figs. 9 and 18 ) are compatible with the expected effects of Zn 2+ ions in all cases, it was shown by detailed NMR analyses of three of the peptides, i.e. , 2, 3, 5 , in the absence and presence of ZnCl 2 , that i ) β ‐peptide 2 forms a hairpin turn in H 2 O, even without Zn complexation to the terminal β 3 hHis and β 3 hCys side chains ( Fig. 11 ), ii ) β ‐peptide 3 , which is present as a 14‐ helix in MeOH, is forced to a hairpin‐turn structure by Zn complexation in H 2 O ( Fig. 12 ), and iii ) β ‐peptide 5 is poorly ordered in CD 3 OH ( Fig. 13 ) and in H 2 O ( Fig. 14 ), with far‐remote β 3 hCys and β 3 hHis residues, and has a distorted turn structure in the presence of Zn 2+ ions in H 2 O, with proximate terminal Cys and His side chains ( Fig. 15 ).